new the newsletter of issue 52 february 2015 bsgm news · 2015. 3. 3. · the newsletter of the...

The Newsletter ofThe British Society for Genetic Medicine

Issue 52February 2015

BSGM News

Human Skin Epidermoid Carcinoma Epithelial Cells (A-431) © Michael W Davidson, National High Magnetic Field Laboratory, Florida State University (http://micro.magnet.fsu.edu/primer/techniques/fluorescence/gallery/cells/a431/a431cellslarge.html)

BSGMRealising Genomics in Clinical Practicepage 2

ACGSSharing genetic variant data across NHSlabs – are we there yet?page 21

AGNCGenetic Counsellor Registration BoardUpdatepage 31

CGSLetter from the President: The times they are a-changingpage 40

CGGConsent and genetic testing: What is goodenough for genomicspage 47

The Newsletter ofThe British Society for Genetic MedicineIssue 52 February 2015

1BSGM News

Chair’s Report Angela Douglas, Chairman, BSGM

From thenewsletter editor

Firstly, it was great to be able to host theBSGM Annual Conference in Liverpooland share the delights of my home Citywith all who attended. Liverpool is a greatCity, not only of culture; but also ofheritage and science, which are at theheart of the City. The conference wasscientifically an overwhelming success,thanks to the excellent organisationalskills of the Scientific Committee and toDina and the BSGM conferencecommittee. The scientific sessions werepacked with state of the art science andthe opening session on Genomics set thebar high for the rest of the Conference.The Session from Health EducationEngland gave us much food for thoughtand Professor Sue Hill was extremelyattentive to the concerns from theaudience about the workforce issues thatare being faced by every workforce groupin Genetics, with a promise that if weprovided the evidence, Professor Hillwould support the profession in findingthe solutions.

The conference seems like a long timeago now and since then most of us havebeen engaged with the GenomicsEngland Invitation to Tender for thepositions of NHS Genomic MedicineCentres. The deadlines have been shortand many, and as the days have becomeshorter the working week for many of ushas become longer in an attempt toprovide the information that would securethe ultimate goal of being one of theGMCs recruiting to the 100K GenomeProject. And as if that has not beenenough to occupy the day job, we have inthe background kept a glancing eye outfor the NHS Genetic Servicesreconfiguration, that has been morphedinto the NHS Genomic ServicesRedesign, with of course no link to theGMCs……only time will tell. At the time of

writing we still have not had sight of theSpecification for the GenomicLaboratories Redesign, that was due togo out to consultation in October. NHSEngland’s Specialised CommissioningGroup sent out the following inSeptember 2014:

“The NHS Genomics Laboratory ServiceRedesign Project has, in line withprocurement practice in the NHS,advertised the project to the wider marketfor providers to register potential interest.This is a standard way to test the appetitein the market for NHS services. Thisprocess is called the Prior InformationNotice (PIN). It does in no way precludeproviders who do not register at thisstage the opportunity to compete furtherin the process when the formal Invitationto Tender is issued. The next stages forthis Project is

• ·The commencement of the 3 monthpublic consultation on the servicespecification in early October

• ·Provider Engagement Event –November

• Issue of ITT – January 2015”

This was followed by the NHS EnglandCommissioning Intentions published thisOctober, stating:

“Genomic and genetic services NHS England is currently completingpreparations to carry out a formalprocurement exercise to support theestablishment of a stronger, moreresponsive, modernised and efficientgenetic laboratory service. This willprovide a new configuration of CentralGenomic Laboratories and will affect bothcurrent regional, local and speciality-based genetic laboratory services. Apublic consultation, clarifying the scope

Welcome to the latest issue of BSGM News.While we have never previously had athemed issue of this newsletter, this could beclassified as the ‘genomics issue’ with manyarticles in the main section of the newsletterdescribing different aspects of genomicmedicine. This theme also carries through tothe newsletters of the constituent groupsdescribing how different aspects of ourmembership will be involved in genomicsnow and in the future.

Our lead article in this issue provides asummary of the PHG Foundation’s reportRealising Genomics in Clinical Practice. Thefindings from this report are timely as manymembers of the BSGM are involved withvarious aspects of the 100,000 GenomesProject and as such will need to consider themany varied and often challenging ethical,legal and social implications of implementingwhole genome sequencing in both a clinicaland research setting.

This issue also contains the first, of hopefullymany, short articles from the newly formedspecial interest group –Dermatogenetics.This group held its inaugural meeting at the2014 BSGM Annual conference and I wouldencourage any BSGM member with aninterest in this area to consider joining thisspecial interest group.

Finally, as this newsletter is for the BSGMmembership, we rely on you to identifytopics that may be of interest to the entiremembership. If you have any ideas for futurearticles or features, please get in touch. Mydetails can be found at the end of the mainsection.

Michelle Bishop


2BSGM News

Realising Genomics inClinical PracticeCorinna Alberg, PHG Foundation

New genomic sequencing technologieshave the potential to revolutionise thediagnosis and treatment of many disorders.The NHS is now on the cusp of introducingnext generation sequencing (NGS)diagnostic tests, including whole exomesequencing (WES) and ultimately, wholegenome sequencing (WGS). Together thesetechnologies will form an important additionto existing genetic testing strategies,promising faster diagnosis of inherited andde novo diseases. The technologies will beparticularly beneficial where simultaneousinvestigation of multiple genes is required,resulting in lower sequencing costs pergene.

But the investigation of the whole exome orgenome brings significant challenges as weattempt to make sense of the huge amountof undifferentiated data these technologiesgenerate and understand the health impactof the vast range of genomic variants –

• The identification of incidental findings(IFs) will raise questions about theirinterpretation and disclosure. Patientsmust be prepared for this eventualitythrough discussion as part of aneffective consent process.

• Variants of unknown significance (VUS)will require clinical and laboratoryexpertise and time to interpret. As thesignificance of many of these variantsbecomes known clinicians will need todecide whether to re-examinesequence data and recontact patientswith clinically relevant new information.

The PHG Foundation’s report RealisingGenomics in Clinical Practice aims toinform the optimal implementation of thesetechnologies and proposes acomprehensive set of recommendationsfor implementing NGS/WGS/WES in waysthat improve healthcare while minimisingpotential harms. It sets out the broadrange of ethical, legal and socialimplications (ELSI) and practical challengesthat will arise from using targetedsequencing using selected gene lists andgenome-wide sequencing technologieswithin a clinical setting.

Background to the Realising Genomics projectThe Realising Genomics project took placebetween 2013- 2014 and comprised offive iterative workshops engaging with awide range of stakeholders andinternational experts. The resultantrecommendations aim to address the ELSIchallenges and resolve some of theoutstanding policy issues including:

• The blurring of the interface betweenclinical care and research as a rapidlygrowing knowledge-base is populatedby both activities and increasing

and draft service specificationrequirements of the new service, willbegin in the autumn. It is anticipated thatthe new pattern of service delivery will bein place in 2016, with a current planned'go live' date of January 2016. NHSEngland is exploring the potential to usethe prime contractor model tocommission the tests for which NHSEngland is responsible via the selectedCentral Genomic Laboratories.

NHS England is a key delivery partner inthe Department of Health-led 100,000genome project. NHS England is currentlyinviting applications from providerswishing to act as NHS Genomic MedicineCentres, which will help identify suitablepatients wishing to consent to participatein the project and provide sample DNA tobe sequenced as part of this importantnational development programme.”

We await the consultation release and thenew specification and will involve ourmembers in our response when that doesfinally happen.

Finally, I would like to take this opportunityto wish everyone a prosperous new year.


3BSGM News

be set up. Mandating deposition of datainto this database whilst ensuringproportionate controls on access will helpcreate a robust and reliable database thatserves the needs of NHS patients.

Systematically collecting evidence of thescientific and clinical validity of geneticvariants is vital to provide an optimalservice, and will also help to clarify thebenefits and risks associated with activelysearching for clinically actionable genes(‘opportunistic screening’).

A recurring theme concerned the volumeof findings that might be generated,particularly VUS. Disclosing findingswithout understanding their significancecould cause distress to patients andfamilies, and delivering that informationcould strain limited resources. Consistentapproaches to generating, interpretingand disclosing these findings will help.Ensuring that new knowledge is availableto inform interpretation and, whereappropriate and with consent, sharedbeyond the NHS, will help to make thesesystems more robust.

Recognising the patients’ autonomouschoices through enhancing currentprocesses for seeking consent will helpmitigate these potential harms. The reportsets out the areas which should beexplicitly addressed with patients in theconsent process, including a thoroughdiscussion of the impact, benefits, risksand uncertainties that arise. The nature ofthe test; the generation, interpretation anddisclosure of IFs and VUS, the sharing ofdata and the potential for reanalysis andrecontact are elements that should beexplicitly addressed. Reanalysis of dataand unsolicited recontact raise novel ELSIchallenges and will require systematicpolicy development.

“A recurring theme concerned the volumeof findings that might be generated”

numbers of patients cross theclinical/research boundary

• Likely changes to the patient pathwayas these technologies becomeentrenched in clinical care and howconsent, disclosure of results andvarious technical aspects should bemanaged to optimise their effectiveclinical implementation

• Developing a framework forimplementing these technologies usinggene lists as a first-line approach.

Summary of key findingsWe have identified the recommendationsthat need be implemented in order fornew diagnostic services using genomicsequencing to be implemented anddelivered in an equitable and ethicalmanner. We have also identified a set ofrecommendations that should beimplemented in order to deliver thesetechnologies in the most efficient manner.The recommendations are alsoconsidered in terms of the ethicalprinciples of beneficence, non-maleficence, autonomy and justice.

We recommend restricting theimplementation of novel NGS diagnostictechnologies to deliberately target analysisand interpretation to those genesassociated with the patient’s presentingphenotype. This can be done throughdeveloping gene lists based onphenotype. Using this approach as a first-line test, before analysing and interpretingthe whole exome or genome, will helpavoid large volumes of data which haveadverse or unpredictable impact.

To support the interpretation ofpathogenicity of genetic variants fromNHS patients, an NHS Database needs to

As with any new technology, ensuringequitable access is a key aspect ofresponsible implementation. Consistentapproaches to patient referrals throughgene lists and systematic approaches toreanalysis and recontact need to bedeveloped. These must be supported byeducation for health professionals andpatients, underpinned by robustmechanisms for evaluation andcommissioning.

These measures will help ensure theresponsible and ethical implementation ofthese technologies, optimising their utilityfor patients and families, minimising thepotential harms and building public trust.

The report is available atwww.phgfoundation.org/project/realising-genomics


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Clinical genome analysis: settingstandards, delivering diagnoses Leila Luheshi, PHG Foundation

include: establishing standards and bestpractice protocols for sequencegeneration, analysis and reporting;improving data-sharing and evidencebase quality; and building necessaryinfrastructure.

Defining the role of a bioinformaticianexplains just what it is thatbioinformaticians actually do and why it isso vital in genomic medicine. Rolesinclude development and maintenance ofalgorithm-based analytical methods,databases, computational tools andworkflows, as well as genomic datamining and interpretation. The briefingalso sets out critical points of contactbetween bioinformaticians and other NHSprofessionals, and poses questions forpolicy-makers and health serviceproviders seeking bioinformaticsexpertise.

Setting the right standards looks ingreater detail at the increasing need for

whole genome sequencing poses a rangeof challenges not necessarily understoodoutside the genetics community. OurClinical Genome Analysis project(http://www.phgfoundation.org/project/wgs/) addresses this; guided by an expertsteering-group, we have created a rangeof resources, which are outlined below,setting out the issues and makingpractical recommendations. Whilst little oftheir content will be revelatory to geneticsprofessionals, they are a valuable meansof communicating with other healthprofessionals, commissioners and policy-makers.

Delivering the right diagnosis examinesthe critical steps in whole genomeanalysis, from raw DNA sequence toclinically actionable diagnostic report,highlighting the potential for variation anderror between different pipelines and theneed for standardisation to ensure thatreporting is sufficiently reliable andaccurate for routine NHS use. Key steps

Many BSGM members will know that ofthe PHG Foundation’s long–standinginterest in the clinical applications ofgenome sequencing; our 2011 reportNext steps in the sequence(http://www.phgfoundation.org/reports/10364/) was the first comprehensiveexamination of the potential clinicalimpact of the rapidly-developing nextgeneration sequencing (NGS) field.

Since then, the NHS operatingenvironment has shifted significantly; withthe establishment of Genomics England,we are now expecting 100,000 genomesto be sequenced by 2017, as a valuablenew resource for cancer, inherited andinfectious diseases. Realisingpersonalised medicine by making genomesequencing and analysis part of everydayclinical practice within the next few yearsis a laudable new goal for NHStransformation. Efforts are underway toprepare for this ‘genomics revolution’ –not least the establishment of a dedicatedgenomics programme for workforcetraining.

However, achieving accurate and clinicallymeaningful diagnoses through the use of


5BSGM News

Service DevelopmentSegmental OvergrowthSyndromes NGS ServiceClaire Langley and Emma Howard, Manchester Centre for Genomic Medicine.

clear and informative report is issuedwithin 40 working days.

Peripheral blood, saliva/buccal and freshtissue samples are accepted for testing,with the latter being the preferred sampletype.

For more information on the SegmentalOvergrowth Syndrome NSG serviceplease contact the laboratory:

Genomic Diagnostics LaboratoryManchester Centre for Genomic MedicineSt Mary's HospitalHathersage RoadManchesterM13 9WLTel: 0161 276 6122

The Manchester Centre for GenomicMedicine is pleased to announce thelaunch of a next generation sequencing(NGS) service for segmental overgrowthsyndromes.

Segmental overgrowth syndromes are aheterogeneous group of rare diseasescharacterised by substantial localised orasymmetrical excessive tissue growth thatcan manifest both at birth and later in life.The umbrella term of ‘Segmentalovergrowth syndromes’ encompassesdisorders such as Megalencephaly-Capillary Malformation (MCM/MCAP)syndrome, Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus (MPPH) syndrome,Congenital Lipomatous OvergrowthVascular Malformations, Epidermal Neviand Skeletal abnormalities (CLOVESsyndrome), Proteus syndrome andCowden syndrome.

Many segmental overgrowth syndromeshave been attributed to mutations ingenes of the phosphoinositide 3-kinasePI3K-Akt signalling pathway, with bothgermline and post-zygotic mutationsassociated. Key genes in this pathway areincluded in the Segmental OvergrowthSyndromes NGS panel, which featureswhole gene screening of PIK3CA andPTEN, as well as targeted screening ofhotspot exons in PIK3R2, AKT1, AKT3,mTOR and CCND2. This test is capableof detecting post-zygotic mutations downto a level of 5%.

This panel uses long range-PCR as thetarget enrichment method and Illumina’sMiSeq system to perform the nextgeneration sequencing. Full bioinformaticanalysis is undertaken and any potentiallypathogenic mutations are confirmed usingSanger sequencing or ARMs-PCR. A

standardisation of approaches to clinicalgenome analysis as demand grows. Thisis essential for delivery of consistent andquality-assured patient care, especially ifthe number of service providers increasesas expected. The briefing also considershow to balance these quality requirementswith the need to maintain serviceaccessibility and innovation.

Sharing clinical genomic data for betterdiagnosis emphasises the urgent need forbetter data sharing across NHSinstitutions. Barriers include disincentives,costs, regulatory concerns and theabsence of sustainable technical solutionsfor depositing and accessing genomicand clinical data. The serious opportunitycosts of failure to act promptly are setagainst proposals for a way forward.These include mandatory data-sharing viaa new, dedicated NHS data repositorythat is simple to use, meets the needs ofclinicians and can interact with 100,000Genomes Project infrastructure, as well asincorporating appropriate consent andconfidentiality measures.

Resources from the Clinical GenomeAnalysis project are available to downloadfree fromwww.phgfoundation.org/project/wgs


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New guidelines for the investigation ofintellectual disability (ID)/ developmentaldelay (DD) in East AngliaLouise Cameron, PHG Foundation and Alasdair Parker, Cambridge University Hospitals Trust

evidence document presents the evidencefrom the literature and regional laboratoryexperience.

Aetiology of ID/DDThe causes of ID/DD are known toinclude biological, environmental andgenetic factors, with many cases beingmultifactorial. Genetic factors areidentified or presumed as the cause ofID/DD in the greatest proportion of cases,with a spectrum of genetic abnormalitiesidentified. Currently around half of casesare described as idiopathic, but newgenomic technologies are impacting onthis and reports in the literature describeincrements in diagnosis rates in patientswith idiopathic ID.1

Genetics and genomics in ID/DDdiagnosisIn line with national policy, the guiderecommends array CGH as a first line testfor this group of patients and isaccompanied with a description of thecapability of the test and the issue ofvariants of unknown significance (VUS).Potential reasons for referral to the clinicalgenetics service are described in secondline testing, along with a discussion oftesting for X-linked ID, including Fragile X.

Initiatives such as the DecipheringDevelopmental Disorders (DDD) projectand Genomics England’s rare diseasecomponent are driving forward theapplication of whole genome and wholeexome sequencing in this area. Whilst stillin the research domain, these initiativesare described in the evidence document,which recommends dialogue betweenpaediatricians and clinical geneticscolleagues to capitalise on the diagnosticpower of next generation sequencing inidiopathic ID/DD. The guide is scheduledto be updated in 2017, by which point the

diagnostic landscape is expected to haveundergone further evolution.

The guides are available to download forfree from www.phgfoundation.org.

Reference1. Baker K, Raymond FL, Bass N.

Genetic investigation for adults withintellectual disability: opportunities andchallenges. Current opinion inneurology. 2012;25(2):150-8.

Finding a diagnosis is important forfamilies and children affected byintellectual disability (ID) anddevelopmental delay (DD); it may help toinform prognosis and care, and inplanning future pregnancies. However, thejourney to diagnosis can be a lengthy andanxious period for parents. In 2013 anonline questionnaire completed by 25consultant community paediatricians inthe East Anglian region revealed variabilityin approach to diagnosis, and somedivergence from the 2006 East Angliandiagnostic guidelines, in part reflecting theincreased use of new genomictechnologies in diagnosis such as arrayCGH.

This year, an updated version of theguidelines has been produced by theguidelines group, which includesclinicians, parents and clinical scientists,and was led by Dr Alasdair Parker,Consultant Paediatric Neurologist,Cambridge University Hospitals Trust. Theguidelines describe the diagnosticinvestigation of children with moderate tosevere ID/DD, and comprise a parents’guide, a clinician’s guide, in the form of adiagnostic flowchart, and an evidencedocument to support the former two. Theprinciple aims of the guides are to:describe best practice in diagnosis,incorporating the latest diagnostictechnologies, and to improve theexperience of parents and children in thediagnostic pathway.

The guidelines group drew on theexperiences and expertise of themultidisciplinary group, to produce guideswhich take account not only of test yield,but also factors such as the severity andpotential treatment for the condition, theimpact of testing on the child and family,and logistics of sample collection. The


7BSGM News

The latest report, Array CGH testing forlearning disability – when is it worth it?,also published on our website(http://www.phgfoundation.org/file/16397/)and presented by lead author Dr GurdeepSagoo to the BSGM conference inSeptember 2014, sets out a cost-effectiveness analysis of using array CGHas a first-line test for learning disabilitywithin a single NHS clinical geneticsservice.

Data was analysed from a cohort of 1,590patients with undiagnosed learningdisability and developmental delay. Theevaluation calculated a statisticallysignificant positive net monetary benefit of£272, estimating that significant efficiencysavings could be made within clinicalgenetics services by moving all array CGHtesting to first line, rather than as a secondline test following a negative karyotype. Acost per positive diagnosis of first linetesting was calculated to be £2,544.42versus £4,819.44 for second line testing.

Further savings in terms of benefits topatients and their families, of making bothmore and earlier diagnoses, were notincluded in this initial analysis, but can beexpected.

Given the advances in DNA sequencingtechnology, economic evaluations areneeded to provide timely evidence in orderto support appropriate uptake of suchadvances into NHS clinical pathways. Youcan read more about this work and itsresults in the short report Array CGHtesting for learning disability – when is itworth it?(www.phgfoundation.org/briefing_notes/353/)

An economic evaluation of genome-widehigh-resolution microarray comparativegenomic hybridisation (array CGH)undertaken by the PHG Foundation - anorganisation focused on the translation ofgenomic technologies into improvedhealthcare services - in collaboration withGuy’s and St Thomas’ NHS FoundationTrust and the UK Genetic Testing Network(UKGTN), shows that moving array CGH toa first line test would result in significantefficiency savings to clinical geneticsservices.

Around 1.2 to 1.5 million people in Englandand Wales have a learning disabilityaccording to the British Institute of LearningDisabilities and Mencap. Compellingevidence exists of the diagnostic benefits ofarray CGH for clinical genetics services.However, the perceived cost andcomplexity of the test, along with lack ofconsensus of NHS service configurationacross laboratories, is hindering moves touse array CGH for routine first-line testingfor cases with idiopathic learning disability,despite UKGTN testing criteria andguidance from professional bodies.

In 2006, PHG Foundation published areport on array CGH in the diagnosis oflearning disability and a sister publication,Parents as Partners. Both reports, availableat www.phgfoundation.org/reports/4968/,were well received by the clinical geneticscommunity within the UK. In the report werecommended that not only should arrayCGH be implemented as a second line testbut that further work should be undertakento evaluate how array CGH would work ina first-line test setting.

New economic evaluationof using array CGH testingfor learning disability Gurdeep Sagoo, PHG Foundation

New YearHonours 2015 –Val Davison MBEThe BSGM is delighted tocongratulate Val Davison, ScientificAdvisor to the National School ofHealthcare Science, who wasawarded an MBE for services togenomic technologies in the NewYear Honours list.

DERMATOGENETICS – a newspecial interest group linking theBSGM with dermatologists


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Dermatogenetics aims to develop linksbetween genetic practitioners with aninterest in dermatology and dermatologistswith an interest in genetics at this criticaltime. We aim to facilitate the sharing ofknowledge and exchange of ideas in bothclinical medicine and research.

Dermatogenetics, as a special interestgroup of the BSGM, aims to help byproviding clinically relevant and up-to-dateinformation for clinical dermatologists aswell as those with an academic interest.

Specifically, Dermatogenetics aims to:

• Improve the recognition andphenotyping of cutaneousmanifestations of genetic disorders, bycloser working between dermatologistsand geneticists.

• Provide a forum at the annual BSGM todiscuss cases that have cutaneousmanifestations at a multidisciplinarymeeting involving dermatologists,geneticists and scientists.

• Offer opportunities for the education ofspecialty trainees in genetics anddermatology via seminars held at theannual BSGM and/or BritishAssociation of Dermatologists (BAD)meeting.

Upcoming meetingsOur next meeting is a half-day event thatwill be held at the BSGM annual meeting in2015.

How to become a member ofDermatogenetics?Membership is open to all individuals withan interest in the clinical and basicscience of the hereditary aspects of skindisease. Expressions of interest should bedirected to Sara Brown or Neil Rajan(contact details below). Dermatogeneticsmembership fees of £30 will beadministered via the BSGM in line withother special interest groups.

Contact us:Sara Brown (treasurer)Clinical Senior Lecturer & HonoraryConsultant Dermatologist ,Dundee [email protected] 01382-381056

Neil Rajan (secretary) Clinical Senior Lecturer & HonoraryConsultant Dermatologist ,Newcastle-upon-Tyne [email protected] 0191-2418813

Striking cutaneous phenotypes represent afascinating aspect of clinical genetics,giving clues to multiple syndromicdiagnoses and valuable opportunity forgaining insight into genetic mechanisms.At this year’s BSGM annual meeting, theinaugural meeting of the Dermatogeneticsgroup followed this theme. Professor CeliaMoss highlighted the range of patterns thatcutaneous mosaicism can present in theskin in her lecture Back to Blaschko. Ourkeynote speaker within the mainconference, Professor John McGrath, gavehis illuminating perspective ongenodermatoses and the role of exomesequencing in the diagnosis and clinicalmanagement of these patients. Talks byjunior clinical academics Sara Brown andNeil Rajan provided an overview of‘dermatology for geneticists’ and ‘geneticsfor dermatologists’.

Perhaps there is no better time to rekindlethe interest in cutaneous phenotyping.Next generation sequencing technologyoffers the promise of identifying genes andgenetic mechanisms responsible for manyof the dermatological syndromes and signswhich remain incompletely understood.The highly ambitious 100,000 GenomeProject, which sets the UK apart as aworld leader at population levelsequencing, will represent a uniquelypowerful resource for the researchcommunity, including rare disease researchin dermatology.


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Milan, 14 patients with metachromaticleukodystrophy have been transplantedwith autologous haematopoietic stemcells (HSCs) that were transduced with alentiviral vector carrying a working copyof the ARSA gene. High-level stableengraftment has been achieved withcorresponding arrest of theneurodegenerative condition. In London,a team led by Bobby Gaspar and AdrianThrasher at University College Londonhave used a similar approach (using agammaretroviral vector containing anoptimised ADA gene) to treat patientswith SCID-ADA. Wiskott-Aldrichsyndrome is also being treated in asimilar way. The use of geneticallycorrected autologous HSCs instead of anallogeneic donor transplant enables aless severe myeloablative regimen to beused and avoids the subsequentproblems of immunosuppression. The riskof graft-versus-host disease is alsoavoided. Plans exist to clinically trial HSCgene therapy approaches in patients withHurler and Krabbe disease.

Two diseases that have been in the genetherapy pipeline for some time are cysticfibrosis (CF) and Duchenne musculardystrophy (DMD). The UK CF GeneTherapy Consortium has recentlycompleted data collection on a multi-dose clinical trial of monthly, nebulised,liposome-based CFTR replacement. Theresults of this trial are eagerly awaited.DMD gene replacement therapy, whichemploys a shortened form of dystrophinknown as microdystrophin, remains fornow at the preclinical stage, albeit withimpressive results in animal models. Onthe other hand, RNA-based therapies forDMD have been in clinical trials for someyears now. The stop codon read-throughdrug Ataluren (now known as Translarna)has been conditionally licensed by the

European Medicines Agency sinceAugust 2014 and its producer, PTCTherapeutics, is seeking to recruitpatients to a confirmatory phase III trial.In addition, trials of two exon-skippingoligonucleotide drugs (Eteplirsen, SareptaTherapeutics; Drisapersen, Prosensa)have been taken to phase II trials. Afterinitial concerns about a lack of clinicalefficacy in the case of Drisapersen’sresults in 2013, a better understanding ofDMD’s natural history together with moreappropriate patient group stratificationhas led to renewed optimism that clinicalbenefit will be achieved with this drug. Incomparison, Eteplirsen-treated boyscontinue to show a sustainedmaintenance of ambulatory ability over atwo to three year period as compared tothe expected natural history course of thedisease.

New technologies are helping to extendthe reach of gene therapy research. Thedevelopment of chimeric antigenreceptors (CARs), which are geneticallyencoded designer antibody-likemolecules expressed by T-cells, allowsthe targeted destruction of tumoursexpressing specific antigens, withaccompanied T-cell clonal proliferationtargeting the same tumour antigen. Up tonow this approach has been pioneeredmainly in the treatment of refractoryleukaemias. However, its application tothe potential treatment of other tumoursis clear. It has been said that genetherapy is only likely to becomemainstream if it can tackle commondiseases. Treatment of cancer wouldcertainly fit this bill. However, it may alsobe possible to treat conditions such asdiabetes by use of genetically engineeredmetabolic sensor-effector implants. Asynthetic biology approach could allowdesign of a genetic circuit whereby a

The European Society for Gene and CellTherapy (ESGCT) hosted its 22nd annualcongress this past October in The Hague,The Netherlands. Earlier in the year thesame venue, the World Forum, hadplayed host to Barack Obama andcolleagues who met there for the NuclearSecurity Summit. Whilst perhaps moremodest in its public and media profile,the annual ESGCT conference isnonetheless also of global significance, atleast to the medical world, and providesan excellent platform and meeting placefor researchers and clinicians with aninterest in novel gene and cell therapies.

The meeting always starts with aneducation and patient day, suitable forstudents, interested patients, cliniciansand others looking for an overview of thesubject. On this occasion an excellentintroductory talk by Len Seymour,University of Oxford, covered the historyof gene therapy from the first human trialfor severe combined immunodeficiencycaused by adenosine deaminasedeficiency (SCID-ADA) immunodeficiencytreatment in 1990 right through to thepresent day. As with the development ofany field, there have been setbacks alongthe way, such as the death in 1999 of18-year old Jesse Gelsinger who wasenrolled in a gene therapy trial forornithine transcarbamylase deficiency.However, the field has neverthelesspersevered and continued to progressand today we stand at a point where anumber of genetic disorders, includingSCID-ADA, X-linked severe combinedimmunodeficiency (SCID-X1), beta-thalassaemia and adrenoleukodystrophy,have all been shown to be treatable bygene therapy.

A growing number of gene therapyclinical trials are currently in progress. In

Gene therapy updateAndrew G. L. Douglas, Wessex Clinical Genetics Service


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NIHR CollaborativeGroup for Genetics inHealthcare – update Siobhan Chan, Genetics Editor, Progress Educational Trust On behalf of the NIHR Collaborative Group for Genetics in Healthcare

glucose sensor expressed by a cellularimplant could be linked to insulinsecretion.

The next ESGCT congress will be inHelsinki from 17-20 September 2015. Forthose interested in the UK gene therapyscene, the British Society for Gene andCell Therapy (BSGCT) has its 2015conference in Glasgow from 9-11 June2015. Both societies are very keen toestablish links with other societies andgroups and BSGM members may wish toconsider what collaborative possibilitiesmay exist.

As a clinical geneticist, I think we oughtto be aware of current gene therapytrials, at the very least so as to be able toinform our patients about them. For thosewho are interested, there is also theopportunity to get involved. Europeanfunding for such research is currentlystrong, with initiatives such as Horizon2020 and the Innovative MedicinesInitiative (IMI) setting aside substantialfunding pots for research into noveltherapies. Indeed, there has never been abetter opportunity to develop genetherapies for rare genetic diseases. Genetherapy is not just a story aboutsomething that may or may not happensome day in the future. It will happen andin fact it is happening now. As aspecialty, I believe we have a chance toplay a central role in the development ofthis field as it takes its first steps towardsbecoming a mature discipline.

1. Practical Research in GeneticHealthcare Session: BSGM Liverpool2014

At the National Institute for HealthResearch (NIHR) Clinical ResearchNetwork (CRN) session at the annualconference of the BSGM in September2014, researchers gave updates on theirongoing studies and appealed for helprecruiting to new studies.

Chair Dr Shane McKee kicked off thesession by highlighting the importance ofgenetics centres helping one another andsharing work, saying it was "pivotal inpulling patients together and coordinatingresearch."

Dr Serena Nik-Zainal was the first tospeak, telling the audience about herstudy into mutational signatures in cancer.(UKCRN 15956:http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=15956) She describedthe way that her team have been workingto find out how the thousands ofmutations present in a cancer genome

arose and matching these to exposure tochemicals such as those throughsmoking, exposure to UV and recurrentinfections.

She detailed the mutational processesthey have already found that "leave acharacteristic mark - a signature - in thegenome" causing normal cells to turn intocancer cells.

The website for the INSIGNIA study isnow up and running(http://www.mutationsignatures.org/insignia), with sections for patients and clinicianswho are involved. They are still looking forparticipants with DNA repair disorders totake part.

Next, Dr Kemi Lokulo-Sodipe spokeabout the launch of the STAARS studyinvestigating Russell Silver syndrome(RSS). This rare childhood-onset diseaseleaves adults with a shorter than averagestature. Dr Lokulo-Sodipe said thatparents are often concerned aboutwhether their children should be treated

Speakers & Chairs: L to R Shane McKee, Gillian Crawford, Kemi Lokulo-Sodipe, DianaBaralle, Serena Nik-Zainal, Lyn Chitty, John Burn & Oliver Quarrell


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“One of the biggest issues in genetic testingat the moment is whether to report backincidental findings”

Dr Quarrell will also weigh up the potentialbenefits of more 'modern' services suchas virtual appointments, which he believesmay be useful for JHD patients who mayfind it difficult to travel.

By having a better understanding of howHuntington's disease develops in thoseunder 20 compared to the adult-onsetdisease, he hopes that doctors will beable to better monitor patients, and "wewill be able to better judge the effect oftherapies and treatments", said DrQuarrell. This study is described in moredetail on page 13.

One of the biggest issues in genetictesting at the moment is whether or notto report back incidental findings (IFs).Gillian Crawford is currently investigatinghealthcare professionals' experiences ofdiscussing IFs with patients.

Her team, based at the University ofSouthampton, have already found that itis challenging for health professionals tobring up this topic. Part of the problem isthat there isn't a standard approach to

the issue of incidental findings amonggenetics services. Having to discusspotential incidental findings alongsidetalking about genetic testing can be"overwhelming".

However, patients were overall "verypositive" about receiving incidentalfindings, giving an example of a familywho were offered regular screening aftertheir child was found to be at higher riskof Lynch syndrome. This study isdescribed in more detail on page 13.

Professor Lyn Chitty gave an overview ofthe RAPID study (UKCRN 5774:http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=5774). She describedthe project's work on non-invasiveprenatal testing (NIPT) for commontrisomies. NIPT has reduced the need forinvasive testing by 80 percent so far, andthe team are now working towards givinga "definitive diagnosis for a wider range ofconditions".

with growth hormone, because it isunknown whether this has an effect onfinal height. By interviewing those withRSS, and taking a medical history, theyhope to be able to provide a definitiveanswer.

"We hope this study will provide moreinformation about whether the treatmentaffects patients' final height, so we canbetter advise these families. This will alsohelp us provide guidance for healthcareprofessionals who work with thoseaffected by Russell Silver syndrome."

They also hope to be able to find thereason why children with RSS haveproblems with eating and are oftenunderweight, but adults are more likely tobe obese. This study is described in moredetail on page 12.

Next to speak was Dr Oliver Quarrell,consultant clinical geneticist at SheffieldChildren's Hospital. His study into juvenileHuntington's disease (JHD) will assesswhich healthcare services are being usedby people with JHD and their carers.

A picture says 1000 words: GenResmembers Louise Nevitt, Miranda Squires &Karen Tricker

GenRes & Speakers


12BSGM News

"Even though it's a long process, thefamilies gain immensely from being a partof research, and I think we should be veryenthusiastic about looking for trials thatour patients could take part in," he said.

This NIHR CRN session was alsoattended by over 20 GenRes geneticsresearch nurses, counsellors andcoordinators who recruit to UK CRNgenetics portfolio studies(http://www.bsgm.org.uk/genetics-healthcare-research/genres/). This was anopportunity for the GenRes personnel tohear about the outputs of the researchstudies where they were involved in therecruitment process and network withGenetics personnel from across the UK.

2. The Russell-Silver STAARS studybegins in UK

Recruitment for the Study of Adults andAdolescents with Russell-Silver syndromein the UK (STAARS UK), UKCRN 16623,is now underway.

Russell-Silver syndrome (RSS) causespoor in-utero growth, short stature,feeding difficulties with a marked lack ofsubcutaneous fat and frequently a broadforehead. The researchers want to knowmore about the rare condition, and findout whether growth hormone treatment isbeneficial to increase the height of thoseaffected.

"It is a rare disease and there is a lotmore to learn. From patients and workingwith the Child Growth Foundation, weknow that patients and their families wantmore information”, said Dr Kemi Lokulo-Sodipe from the University ofSouthampton, speaking at the annualconference of the British Society ofGenetic Medicine.

Children with RSS often have problemswith eating, as they may have an aversionto food, a cleft palate, lack of appetite,and/or gastrointestinal reflux. But adultsgenerally have fewer issues and,conversely, may become overweight inlater life. Part of the research will involveinvestigating why this is the case, andinterviewing the patients to ask if andwhen eating habits and preferenceschanged.

Children who are small at birth and do not‘catch-up’ in their growth at four years oldcan be given growth hormone treatment,which involves daily injections for up toten years. As stated by Dr Lokulo-Sodipe,"for parents of children affected withRussell-Silver Syndrome, it can be hard todecide whether or not to treat theirchildren with growth hormone. We hopethis study will provide more informationabout whether the treatment affectspatients' final height, so we can betteradvise families. This will also help usprovide guidance for healthcareprofessionals treating patients with RSS."

In 60-70% of RSS cases an underlyingepigenetic cause is found. In 50-60% thecause is hypomethylation at the imprintingcontrol region at chromosome 11p15. In5-10% maternal uniparental disomy ofchromosome 7 is found.

The researchers aim to recruit 100patients with RSS who are aged 13 yearsand above. A single study appointmentinvolves a review of their medical history,examination, blood and genetic tests,height, weight and body compositionmeasurements. Approximately one third ofthe participants will be invited for an in-depth interview about their experience ofliving with RSS. "We plan to speak topatients with RSS to find out how their

Patients and healthcare professionals are"universally positive" about NIPT: theyvalue the safety and appreciate earlierdiagnosis, she added.

Professor Chitty thanked audiencemembers for their contributions to thestudy's sample bank, saying it was“absolutely critical” to the success of theresearch. By the end of 2014, non-invasive testing should be available inmore than 60 countries.

She also spoke about the EACH study,which is now being prepared forpublication (UKCRN 11729:http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=11729). Thetechnique, using array CGH for detectingfetal chromosomal abnormalities, meantan extra eight percent of chromosomalabnormalities were found over using NIPTalone. "The majority of chromosomalabnormalities would be missed if wedidn't have a whole-genome approach,"said Professor Chitty.

The session was rounded off by ProfessorJohn Burn, who announced that theCAPP3 study was seeing its first patients,and that the definitive 10-year follow-upstudy for CAPP2 is due next year.

He described how the NIHR ClinicalResearch Network is crucial to suchresearch trials, both in terms of helping torecruit patients and developing registries.Despite the effort involved in setting upclinical trials, he said, it was worthwhile tokeep going because of the huge potentialbenefits for patients.

Professor Burn reminded the audience ofthe research that has allowed somegenetic disorders to become treatable,most notably phenylketonuria and familialadenomatous polyposis.

“This NIHR CRN session was also attendedby over 20 GenRes genetics research nurses,counsellors & coordinators who recruit toUK CRN genetics portfolio studies”


13BSGM News

“The families for whom incidental findingswere found were keen to receive thisinformation”

Crawford. "We found a lot of variation:some talked about it in reasonable detail,some mentioned it very superficially, andsome didn't mention it at all."

Ms Crawford suggested that the sheeramount of information that HCPs couldgive to patients and their relatives isoverwhelming. Whilst technologies are stillchanging rapidly and debates about whatincidental findings are looked for continue,it can be difficult for HCPs to know whatthey should communicate. Also, once anincidental finding is found, the interpretationof its significance may depend on otherfactors, for example, information about thefamily history, and HCPs found thissituation tricky, particularly if theyconsidered this information would be ‘outof the blue’ for patients and their families.

However, the families for whom incidentalfindings were found were keen to receivethis information, the study reported. "Thefamilies talked very positively about havingreceived this information: it was helpful andthey could access interventions," said MsCrawford. "Even if treatments weren'tcurrently available, they hoped they wouldbe in the future. They found it empoweringto have the information."

Ms Crawford spoke about a patient whosegenetic testing revealed that he had aLynch syndrome mutation. His fatherdescribed the finding as a "lucky break"because it meant his son could receiveregular screening.

Around one percent of array CGH tests willreturn an incidental finding, but this figurecould be much larger for, exome and wholegenome sequencing.

The second stage of the study is due tostart soon, around 300 healthcare

professionals will be asked to detail theirviews on the consent to and disclosure ofincidental findings in a questionnaire. "Thispart of the study will focus more on whotakes consent, what they think this processshould include, how broad or specific thediscussion should be, and what choicesshould be given to patients about howmuch is disclosed," said Ms Crawford.

This UKCRN portfolio study 10917,Incidental Findings (IFs) from genetic testsis funded by a NIHR Clinical DoctoralResearch Fellowship to Gillian Crawford

http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=10917

4. Patients needed for JuvenileHuntington's disease study

Researchers at Sheffield Children'sHospital are recruiting patients for a studyinto juvenile Huntington's disease.

Dr Oliver Quarrell, consultant clinicalgeneticist, and his team want to seewhich healthcare services are being usedby people with JHD and their carers.

People with Huntington's disease developsevere problems with movement andbehavioural problems that worsen as thedisease progresses. It is a life-limitingcondition that typically begins inadulthood. Those who develop symptomsbefore the age of 20 are said to haveJuvenile Huntington's disease (JHD).

"It is recommended that people withHuntington's disease should be cared forby a multi-disciplinary team, but thereisn't a lot of evidence for this," said DrQuarrell. "We want to know how best tocare for people with this condition."

condition affects them and how it'schanged throughout their lifetime," saidKemi Lokulo-Sodipe.

For more information please email:[email protected] .

Further information about this study, Studyof Adults and Adolescents with RussellSilver syndrome in the UK is available at:http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=16623

3. Health professionals need support inmanaging incidental findings

As technology for genetic testing improves,the chance of finding unexpected resultsincreases. Discussing Incidental Findings(IFs) with patients and their families is agrowing concern for clinicians, a study hasfound.

Gillian Crawford and her team at theUniversity of Southampton(www.cels.soton.ac.uk) spoke to 16 familymembers and 32 healthcare professionals(HCPs) across the UK about their viewsand experiences about incidental findingsfrom genetic tests. While families weremostly keen to hear about these results,healthcare professionals found their clinicalmanagement challenging, the researchfound.

The study also found that practice variesconsiderably and that many HCPs do notroutinely tell patients about the possibility ofincidental findings before testing takesplace, and thus do not take specificconsent for reporting these findings.

"Centres around the country have their ownforms and their own care pathways, andthere was no standard approach to theissue of incidental findings," said Ms


14BSGM News

progression rate. "As well as collectingpatients together for this study andfinding out the best way of organisingservices, I hope we can use it to addressthe other questions which are unclear,"said Dr Quarrell.

"This is a tremendous opportunity togather all the cases of JHD in the countrytogether, but to do that we need thesupport of the clinical geneticscommunity," he added.

The team are asking clinicians to checkgenetic databases to find patients withmore than 50 CAG repeats in theHuntington's gene and identify those whohad an onset less than 20 years. They arehoping to interview 12 families and sendquestionnaires to the others. 30 responsesto the questionnaires are required. Theteam will also interview up to 40 healthcare professionals who currently look afterpatients/families with JHD.

Further information about this studyUKCRN 17578, Services for JuvenileHuntington's Disease is available at:http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=17578

Dr Quarrell and his team will investigatewhether a 'one-stop' clinic would bebeneficial to JHD patients and theircarers. He also suggests that 'virtualclinics' could be of use to the patients, asit will mean they will not have to travel –something that can be a problem forthose with a movement-limiting disease.

Specialist clinics are available for peoplewith adult-onset Huntington's disease,who may need the help of speechtherapists and physiotherapists. But thesemay not always be suitable for those withJHD as they may require differentexpertise, such as paediatric neurologistsor child psychologists.

The team also hope to develop a ratingscale to provide a better assessment ofdisease progression in people with JHD."Having a better way to monitor thepatients' condition will mean we will beable to judge the effect of therapies andtreatments," said Dr Quarrell.

The researchers say there is a lot aboutJHD which is not yet understood, such aswhether juvenile onset leads to a shorterlife expectancy, or a faster disease

Further information on portfolio studies can be found on the UK ClinicalResearch Network (UKCRN) Portfolio Databasehttp://public.ukcrn.org.uk/search/. If you think your research could benefit fromthe NIHR Clinical Research Network: Genetics services visit

http://www.crn.nihr.ac.uk/about_us/genetics/

or email Dr Gill Borthwick, the Genetics National Research Coordinator, [email protected]. These articles were prepared by the ProgressEducational Trust on behalf of the Collaborative Group for Genetics inHealthcare (CGGH), working with the NIHR Clinical Research Network:Genetics. For further information on the Collaborative Group for Genetics inHealthcare (CGGH) visit http://www.bsgm.org.uk/genetics-healthcare-research/

“The researchers say there is a lot aboutJuvenile Huntington’s disease which is notyet understood”


15BSGM News

Glasgow University MSc MedicalGenetics Teaching Team win UKProspects Postgraduate Award

Professor Tobias is lead author ofundergraduate and postgraduate textbookson medical genetics and is ChiefInvestigator of a Wellcome Trust fundedresearch project involving exomicsequencing for rare disorders. He has wonfour personal teaching awards since 2012,including three Student RepresentativeCouncil awards from students themselves.In addition, the Glasgow MSc MedicalGenetics teaching team have together wontwo other university awards for teachingexcellence in 2014. The internationallypopular MSc programme includes courseoptions on Genomics and on CancerSciences and it receives much invaluableinput from NHS clinicians and clinicalscientists.

The MSc Medical Genetics at the Universityof Glasgow has recently won the title ofBest Teaching Team (Science, Engineeringand Technology) in the UK-wide 2014Prospects Postgraduate Awards. Theaward was collected by BSGM member,Professor Edward Tobias (HonoraryConsultant in Medical Genetics and ClinicalDirector of the course), and by Dr MariaJackson (Senior University Teacher andcourse Programme Director). The glitteringawards ceremony, on 10 November 2014,at The Midland Hotel in Manchester, wasattended by more than 150 leaders inpostgraduate education provision.

Nominations for these prestigious teachingawards were made by students, and theentries were judged by a ten-memberpanel that included representatives fromthe National Union of Students, the UKCouncil for Graduate Education, the HigherEducation Academy and the HigherEducation Funding Council for England.

David Walker, a student who is to graduatewith his MSc in Medical Genetics inDecember 2014 said: “I am so pleased forthe Medical Genetics team to berecognised for their excellence – not justinternally, at the University, but across thecountry. The team bring a unique personaltouch to the course and complement eachother’s strengths, providing one of the mostenjoyable experiences I’ve had during myfive years at the University.”

The Prospects Postgraduate Awards,sponsored by University Business, areannual accolades solely dedicated tocelebrating best practice in teaching andthe most exciting developments in UKpostgraduate education. Prospects, theUK’s leading postgraduate educationpublisher, maintains the officialpostgraduate course database. TheProspects Chief Executive said: “It’sfantastic to see such a high calibre ofentries from the UK’s leaders inpostgraduate education. Each year we’reoverwhelmed by the support andexcitement we receive. Congratulations tothe Medical Genetics team who havedemonstrated a wide breadth of ways tosupport their students.”

PsychiatricGenetics forGeneticCounsellors


16BSGM News

Peer support for peoplewith a family history ofbreast cancerNik Thoren, Breast Cancer Care

have to walk alone. I was fortunate to bewell supported by my genetics team, butthrough the years I’ve met other womenin a similar position and realised noteveryone has that support. I ampassionate about supporting otherwomen through the Someone Like Meservice, to help ensure no one feelsthey’re alone when faced with bigdecisions about their future.”

To access the Someone Like Me service,people can call 0345 077 1893, [email protected] text SLM and their name to 07889001289.

For further information about the servicevisitwww.breastcancercare.org.uk/someonelikeme

In February, the Translational Genetics Groupat Bournemouth University is running a twoday intensive workshop titled: PsychiatricGenetics for Genetic Counsellors. Researchcarried out in Canada by Dr JehannineAustin’s group at the University of BritishColumbia has shown that people withpsychiatric conditions and their families areinterested in receiving genetic counselling.However, research has also demonstratedthat there are barriers obstructing cliniciansfrom providing genetic counselling servicesfor this population.

In this two-day workshop, a group of 20learners will receive intensive, practically-oriented instruction and support designed toincrease confidence and competence withproviding effective genetic counsellingservices for people with psychiatric disordersand their families. Topics include: orientationto psychiatric diagnoses, in depth review ofthe genetics of psychiatric disorders, therelationship between explanations for causeof illness and stigma, psychosocial issuesthat attend changing patients’ explanationsfor cause of illness and strategies formanaging them.

Funded by Bournemouth University’s FusionInvestment Fund and facilitated by KevinMcGhee PhD and Jehannine Austin PhDCGC/CCGC, this workshop will also serveas a platform to establish a network ofindividuals who can lead the consolidation ofthe emerging area of psychiatric geneticcounselling as a specialist geneticcounselling practice area within the UK.

Demand is high; already we have hadregistrations from the UK, Israel, USA,Norway, Germany and Romania. Membersof the BSGM interested in further informationon the field of psychiatric genetics areencouraged to [email protected] for furtherdetails.

Breast Cancer Care’s unique SomeoneLike Me service has further expanded thesupport it offers.

The service, which provides support overthe phone from trained volunteers forpeople affected by breast cancer, nowoffers the opportunity for people whohave a faulty BRCA gene to speak tosomeone with a similar experience. Thiswill give anyone worried about theirsituation the chance to talk openly withsomeone who understands how they maybe feeling.

Since it was founded more than 40 yearsago, peer support has been central partof Breast Cancer Care’s work. This latestdevelopment is the result of an increase inthe number clients wishing to speak tosomeone about their experience ofgenetic testing and making decisionsabout risk-reducing treatments.

Jackie Harris, Clinical Nurse Specialist forFamily History and Breast Health atBreast Cancer Care, said: “We are reallyhappy to now offer tailored support tothose facing difficult decisions aboutfamily history through Someone Like Me.We work alongside a number of geneticcounsellors and geneticists around thecountry when developing our healthcareprofessional training, patient informationand patient services. We look forward toworking more closely with geneticcounsellors and are so grateful to ouramazing volunteers providing this vitalemotional support.”

Jo is one of the new Someone Like Mevolunteers. She said: “I was told I had theBRCA1 altered gene nine years ago at theage of 30. My sister was given the allclear from the genetic testing, which leftme feeling like it was a road that I would

Conference reportEuropean Society of Human GeneticsMilan, Italy. May 31 – June 3 2014Harsh Sheth- PhD student, Institute of Genetic Medicine


17BSGM News

This year, our Annual General Meeting willtake place during ESHG 2015 in Glasgow.

1. Chairman’s Report

2. General Secretary’s Report

3. Treasurer’s Report

4. Conference Organiser’s Report

5. Any other business

If there are any matters which memberswish to raise would they please send themto the General Secretary, Dr Adam Shaw,Clinical Genetics, 7th Floor Borough Wing,Guy's Hospital, Great Maze Pond LondonSE1 9RT by Monday 4 May 2015

email: [email protected]

I was awarded travel grant to attend theEuropean Society of Human Genetics2014 conference in Milan, Italy. Theconference discussed latest trends,technologies and clinical applications invarious areas of human genetics. Myabstract titled Polymorphism in genesCYP2C9 and ODC1 involved in aspirinhandling influence colorectal cancer riskwas selected for poster presentation. Theposter presented results of investigatingthe impact of 32 SNPs in 9 genes oncolorectal cancer (CRC) risk using theLeeds Colorectal Cancer Panel, whichcontained 1910 cases and 1276 controls.The novel data indicated a significantinverse association between the minoralleles of 2 SNPs in the ODC1 gene withCRC risk. Upon stratification by cancersite, minor allele of a SNP from ODC1and CYP2C9 gene showed inverseassociation only with colon cancersuggesting site-specific influence. The

ESHG 2015

June 6-9, 2015

At the SECC in Glasgow in conjunction with the British Society for Genetic Medicine.

Annual GeneralMeeting

Noticeboard

poster received attention from severalnoted peers and colleagues such asProfessor Andrew Read while a groupfrom University of Helsinki showed interestin collaborating to validate ourepidemiological results. Apart from thetalks presented by eminent scientistssuch as Professor Mario Capecchi andProfessor Sir Michael Stratton, theconference conducted an interactivedebate titled What IF… (IncidentalFindings) where different approachesdeveloped by the societies from bothsides of the Atlantic for counsellingpatients for ‘incidental findings’ weredebated. In the end, I would like to thankmy supervisors Professor Sir John Burnand Dr. Mike Jackson for their unwaveringsupport and guidance and to the BritishSociety of Genetic Medicine for awardingme with the travel grant to attend theconference.


18BSGM News

Welcome toNew Members

64 new members were accepted by theBritish Society for Genetic Medicine in Juneand September 2014.

Miss Nazya Azem CGSDr David Brawand BSGMMiss Celia Brown Lab TraineeDr Andy Buckton ACGSDr Anne-Cecile Burgeire Lab TraineeDr Ruth Carey-Heaton AGNCMiss Heather V Chalinor AGNCMiss Fiona Chamberlayne AGNC Dr Graeme Clark BSGMMiss Trudie Cottrell Lab TraineesDr Anthony Dallosso Lab TraineeDr Esther Dempsey CGSDr Natalie A Forrester Lab TraineeMr Pierre Foskett ACGSMiss Tamsin Gannon CGSMrs Gael Ganz AGNCDr Nicole Gassan Lab TraineeDr Gabriella Gazdagh CGSMrs Louise Gillies AGNCMs Joana T G A Gomes AGNCMrs Jennifer Gorrie AGNCMrs Elspeth M Graham AGNCDr Mark J Hamilton CGSMr Eoin Hanney AGNCMrs Claire Hodgkiss ACGSDr Caroline Hutchison CGSMiss Rachael E Irwin Lab TraineeDr Shatha Janabi CGSMiss Sian Jenkins AGNC Dr Rachel Jones CGSMr Garan H L Jones ACGSMs Areeba Khan AGNCMs Kelly Kohut BSGM Miss Emily Lamb AGNCMiss Frances Lane AGNCDr Laura Lopez Pascua Lab TraineesProf Irwin Maclean BSGMMr Robert J Macleod ACGSDr Rowena Mitchell Lab TraineeDr Dylan Mordaunt CGSProf Azim Nejatizadeh ACGSMiss Katie Nelson AGNC

Mr Rodney Nyanhete Lab TraineeDr James O'Byrne CGSDr Alisdair Philip AGNCMiss Ellen M Quinn AGNCMs Belinda Rahman AGNCDr Sara Rey Lab TraineeDr Ruth Richardson CGSDr Elaine Robertson ACGSMiss Antoniya Ruseva AGNCDr Gavin Ryan Lab TraineesDr Gurdeep Sagoo BSGMDr Schaida Schirwani CGSMiss Claire Shea-Stokes AGNCProf Mohammed Shekari ACGSDr Sivagamy Sithambaram CGSProf Philip Staniere BSGMMiss Anna Tanska ACGSDr Janet Taylor BSGMDr Mikel Valganon ACGSMr Marc Wadsley Lab TraineesMiss Elizabeth Watson Lab TraineesMiss Sinead Whyte AGNC


19BSGM News

Direct Debit Subscriptions for2015/2016

The membership subscriptions will be collected by direct debit during 5-7 April 2015 (see table below for breakdown for each constituent group)

For UK Members: Preferred option for payment is by Direct Debit but this is onlyavailable for bank accounts within the UK.

Note: Please be aware that methods of payment other than Direct Debit will incur anadditional £5 charge. This is not applicable to Overseas Members.

For those members who do not pay by direct debit the Society will be contacting youshortly. Membership Subscriptions are due on 1 April 2015, all payments to be receivedby the end of April 2015.

Affiliate Membership of the European Society of Human GeneticsFor those members who have also opted to take out affiliate membership of the ESHGan additional fee of £44 will also be collected – please note that this rate has notchanged as per 2014/2015 through negotiations.

Your ESHG membership will be renewed if subscribed through BSGM unless we arenotified by yourselves otherwise before the end of March 2015.

SubscriptionBSGMonly

ACGS AGNC CGSGeneticLaboratoriesTrainees

CGGonly

DGonly

BSGM component 55 40 40 40 40 40 40

Payable toConstituent Society

- 15 25 25 15 15 15

TOTAL 55 55 65 65 55 55 55

Cancer GeneticsGroup

- 15 15 15 15 - 15

DermatogeneticsGroup

- 15 15 15 15 15 -

TOTAL includingCGG membership

- 70 80 80 70 - 70

TOTAL includingDG membership

- 70 80 80 70 70 -

TOTAL includingCGG and DGmembership

- 85 95 95 85 - -


20BSGM News

BSGM News Editor

Deadline for contributions for nextissue is 30 April 2015

BSGM Editor: Michelle Bishop PhD

National School of Healthcare ScienceHealth Education West MidlandsSt Chads Court213 Hagley RoadEdgbastonBirminghamB16 9RG

Email: [email protected]

Forthcomingconferences

(CGS) Clinical Genetics Society SpringConference 2015: 03 March 2015Venue: Royal College of Physicians, 11 St Andrews Place, London NW1 4LEContact: [email protected] Website:http://cgs2015.bshgconferences.org.uk/

Dysmorphology Meeting: 04 March 2015Venue: 33QS lecture theatre at the NationalHospital for Neurology and Neurosurgery, 33Queen Square, London WC1N 3BGContact: [email protected] Website:http://cgs2015.bshgconferences.org.uk/

(CGG/ IMPAHC) 14th InternationalMeeting on the Psychosocial Aspects ofHereditary Cancer, in Conjunction withthe UK Cancer Genetics Group SpringMeeting 2015: 05-07 May 2015Venue: Manchester Conference Centre,Sackville Street, Manchester M1 3BB, UKContact: [email protected]:http://cgg2015.bshgconferences.org.uk/

(ESHG) European Human GeneticsConference: 06-09 June 2015Venue: SECC, Glasgow, Scotland, UnitedKingdomContact: [email protected] Website:https://www.eshg.org/eshg2015.html

(ASHG) American Society for HumanGenetics Annual Meeting: 06-10 October2015Venue: Baltimore, Maryland, USAContact: [email protected] Website: http://www.ashg.org/2015meeting/

In addition to the events listed above, detailson other courses and conferences of interestcan be found on our website:http://www.bsgm.org.uk/news-events/events/

Association for Clinical Genetic Science

A member of the British Society for Genetic Medicine


We thought we were getting close whenGraham Taylor’s vision of DMuDb, adatabase of mutations reported bydiagnostic genetic laboratories, becamereality through the National GeneticsReference Laboratory (NGRL Manchester)funding. Andrew Devereau’s team workedhard to establish the infrastructure andsupport laboratories to upload their data.The result was 51,575 variant reports from219 genes as of March 2014. But then themoney ran out and the future looked glum.Fortunately DECIPHER has come to therescue, an online database of geneticvariation and associated phenotypicinformation in patients with rare disordersbased around an interactive genomebrowser (https://decipher.sanger.ac.uk).Originally set up in 2004 to capture copynumber variation, DECIPHER has beenexpanded to also include single nucleotidevariants and small insertions/deletions.

The Exeter Genetics Laboratory providesgenetic testing for >75 rare disorders sofinding novel variants is a frequentoccurrence. Databases like EVS(http://evs.gs.washington.edu/EVS/) andExAC (http://exac.broadinstitute.org/) canbe useful but even better is the knowledgethat another diagnostic laboratory hasidentified patient(s) with the same variant. In2012 and with the help of an excellentwork experience student, Kelsey Loudon,we embarked on a project to upload allpathogenic/likely pathogenic and variantsof uncertain clinical significance reportedbetween 1996 and 2010 into DMuDb.Kelsey handed the baton to SophieRobertson, Annabelle Whatmough, andHannah Jones who assisted with theannotation of data stored within StarLIMSfrom 2010. We are very grateful to JawaharSwaminathan who transferred our datafrom DMuDB and uploaded the additionalvariants from StarLIMS. In total we have

21ACGS News

Editorial

excellent cutting-edge reports. First upare two articles with a common theme:sharing genetic (sequence change)information. Perhaps the most obviousquestion is why, after two or threedecades, do we appear to be no closerto a common solution. Too manydatabases, people!

Next up is Ian Berry’s excellentarticle/advertisement for Leeds’ NGSservice, which looks very impressive.Nice to see Primary Ciliary Dyskinesiafeature in the mix; an active interest in aprevious life.

Caroline Sarton then gives us aconference report on sudden cardiacdeath, followed by a briefreview/advertisement of Oxford’sCardiac Arrhythmia Panel. It’s veryimpressive that the lab has been able toapply this to tissue from paraffin blocks,thus enabling retrospective familystudies to be carried out.

It’s encouraging to receive an articlefrom a Genetic Technologist, and wehave one such in the form of a reportby Emma Clark on the recent GTmeeting.

Finally, Carolyn Tysoe and others fromExeter show the way towards apaperless office, describing theirsuccess in emailing genetic reportsusing StarLims. Further congratulationsare due to them for sneaking the word‘postpeople’ past the editors!

Martin Schwarz

As we go to press, Leicester geneticistsspill the beans on Her Majesty theQueen’s ancestry and posit theexistence of a blue-eyed blondeRichard III. This could all be cleared upwith a few royal exhumations, (whichwon’t be happening any time soon!).Our Royals are not overly keen ongenetic investigations (Richard III’sskeleton being not the only one in thecupboard) although HRH The Duke ofEdinburgh did supply a DNA sample forJean-Jacques Cassiman’s investigationof the ‘Ekaterinburg’ bones of TsarNicolas and his family, Prince Philipbeing related to the Tsarina Alexandra.Nevertheless the Leicester (and others)study shows the power of patrilinealand matrilineal investigations using Ychromosome and mitochondrial DNAstudies respectively.

Also in the news, 23andMe haveanother go at launching their DNAscreening test, after it was banned inthe US. One of its sponsors is Google,and since the saliva test tubes have tobe sent to the Netherlands before beingtested in the US, one could be forgivenfor asking which country will be theeventual recipient of any tax paid.23andMe has now hired a dedicatedteam working on obtaining FDAapproval.

And so to this bumper issue of theACGS section news and many thanksto all those contributors who haveslaved away over a hot sequencer orendured hours of conferencepresentations, to bring us some

Sharing geneticvariant data acrossNHS labs – are wethere yet?Andrew Parrish, Melissa Sloman, MartinaOwens and Sian EllardExeter Genetics Laboratory

Let’s start with the positives: when wetalk about sharing genetic variation datawe are standing on the shoulders ofgiants. We have the human genomeassembly,1,2 now at version 38. It is stillnot formally complete, but represents aframework on which to anchor themajority of genetic loci. We also havegenome variation descriptions in formsfamiliar to clinicians (HGVS nomenclature)and to basic geneticists (VCF) anddatabases like LOVD that can work withboth systems. Because the scale of dataoutput from modern sequencers it isbecoming self evident that an essentialway of attaching meaning and value tothose data will be to share the variantinformation both from other cases andfrom different centres. Much of this canbe obtained from international resourceslike HGMD, Exac and ClinVar, but some ofthe data may be associated with clinicalrecords, so whilst sharing can and doesbenefit patients, especially those with rarevariants of unknown significance, it mustbe done in a way that protects patientand research confidentiality.

As laws and medical practice affectingdata sharing are country-specific; nationalnetworks are a logical way forward.Australia has taken steps in this directionwith a national database (seevariome.info) roughly analogous toDMuDB, open to registered participantswith 12 participating labs, over 30,000instances and over 900 unique variantsrecorded. But it is a sobering thought thateven a single exome case would generate20 to 100-fold more variants. Incentivisinglabs to share their data has never beeneasy. It is often seen as an additionaloverhead for services already underpressure. Yet participation in nationalnetworks could become a requirement forlaboratory accreditation in Australia and

now submitted 2970 variants from >50genes to DECIPHER.

The genetic variants are stored within theDECIPHER NHS data-sharing project. Thislimits viewing rights to other NHS geneticslaboratories who can see which lab hasidentified a variant of interest and contactthem directly. Data are submitted inpseudonymised format with the internallaboratory number and laboratory as theidentifiers. This is a first step towards globalgenomic data sharing (see the GlobalAlliance for Genomics in Health websitehttp://genomicsandhealth.org/).

For the continued success of this project, itis important that the benefit gained fromsharing data between laboratories isgreater than the effort required to upload.With this in mind, we have set up an exportfrom StarLIMS and use the Mutalyzer(https://mutalyzer.nl) bulk position convertertool to convert our variant positions togenomic coordinates to conform to theformat required by the automatedDECIPHER upload tool. We will run this ona monthly basis in order to keep up to dateuntil our dream of live data export/uploadto DECIPHER becomes a reality. If otherlabs are contemplating similar mutationuploads then we’d be pleased to share ourexperience as the full benefits will only berealised when sharing these data becomesroutine practice. Why not get a head startnow before genetic variant sharingbecomes mandatory?




22ACGS News

Developing a network forsharing genetic variant dataacross Australia & NewZealand: lessons from overseas?Graham Taylor, Desiree du Sart & John-Paul Plazzer, Victorian Clinical GeneticsLaboratories, Murdoch Childrens Research Institute, Victoria, Australia

elsewhere and we will be followingdevelopments overseas with interest.Accreditation will push the database froma laboratory filing system into the realm ofmedical information, subject to qualitycontrol and assessment as discussedrecently by a joint group from the HumanVariome Project and the Royal College ofPathologists of Australasia.3 Althoughmuch of this work may need to take placewithin a national framework, internationaldata sharing standards would ensure theoption of wider data exchange whereappropriate, aligning with the vision of theGlobal Alliance for Genomics in Health.

We hope that genetics services acrossthe world will take the advice expressedby our colleagues from Exeter and get ahead start in genetic variant sharing.

References

1. International Human GenomeSequencing Consortium (2001) Nature409, 860-921

2. Venter et al (2001) Science 291, 1304-1351

3. Bennetts et al (2014) Applied &Translational Genomics 3, 54–57




on two different SureSelect reagents, bothrun on our Illumina HiSeq pipeline.³ Firstly, acustom panel of approximately 400 genes oflocal clinical interest, the Selected Gene or‘SelGen’ panel (alternative working titlesincluded ‘YourGene’ and ‘Leeds-ome’…),which is ideal for selective analysis ofphenotypically-defined, static panels of 2-50genes. Secondly, targeted gene analysis ofwhole exomes. The analysis and reportingpipeline is summarised in figure 1. Thedisease panels currently offered orundergoing validation are summarised intable 1.

Use of this two-pronged approach hasseveral advantages. The smaller custom‘SelGen’ panel is somewhat analogous to aclinical exome (a third approach which weare currently validating), but offers reducedsequence run costs (less than half of ouranticipated clinical exome sequencing costs)and more comprehensive coverage (of the734 exons covered in the diagnostic servicesvalidated thus far, 730 [99.5%] areconsistently covered to a read-depth of 30Xin all samples tested). Focussing on asmaller subset of the clinical exome allowsus to “play to our strengths” of clinical andscientific expertise (specialising rather thangeneralising). It also avoids the unnecessaryamplification of 4000+ genes, the vastmajority of which cause vanishingly rarediseases unlikely to ever be encountered inthe clinic, with the associated implications ofcost and potential incidental findings. Wehave designed the gene list such that wecan easily expand our current serviceportfolio into related areas of interest.

In contrast, whole exome sequencing (WES)is applied to highly heterogeneous and/orrapidly evolving areas of genetic disease. Withour local interest in recessive ciliopathydisorders, we have focussed thus far onprimary ciliary dyskinesia (PCD) and theoverlapping Meckel and Joubert syndromephenotypes, offering targeted panels for each.

23ACGS News

Next-Generation Sequencing for Infantile-and Paediatric-Onset Genetic Disease:Evolution of the Leeds ApproachIan R Berry, Yorkshire Regional Genetics Service.

However, it soon became clear that thisapproach lacks scalability, can introduceamplification artefacts, and, perhaps mostcrucially, can be severely affected by inter-sample variability in extraction andresuspension protocols (a particular problemfor labs receiving a wide range of out-of-areaand overseas referrals). A recent comparisonof our PCR- and hybridisation-basedtargeting protocols for 19 different genesacross eight typical samples revealed amean exonic ‘drop-out’ rate of 6.4 exons forthe PCR approach, and only 0.8 exons for ahybridisation-based approach (AgilentSureSelect). Further scrutiny of the exonfailures indicated a far more consistentpattern of sample-to-sample coverage in thehybridisation-based libraries, with coveragedeficiencies present in just three differentexons, compared to 14 different exons in thePCR-based method.

Development of hybridisation-basedtargeting techniques began in Leeds in2011. Following comparison of the AgilentSureSelect and HaloPlex chemistries, webegan diagnostic work-up on SureSelect, asit offered better on-target coverage, reducedinter-sample variability, and reportedlydelivered more accurate allele ratios/fewerPCR duplicate artefacts. Our firstdevelopment was a service for all 82heritable cancer genes,² from whichphenotype-specific sub-panels can beselected on referral. The first diagnosticreports were issued in April 2013.

We are now developing diagnostic servicesfor paediatric- and infantile-onset disorders

Of the many challenges that the next-generation sequencing (NGS) revolution hasposed to diagnostic service laboratories, thechoice of gene enrichment technique hasperhaps generated the widest range ofsolutions across the discipline. In Leeds, wehave developed services using a three-pronged strategy (see table 1) to give thebest balance of cost, coverage and scalabilityin different disease modalities. This is bestillustrated by the evolution of our infantile andpaediatric non-cancer disease services.

Validation of NGS in 2009, based initially onlong-range PCR amplification of targetgenes, library preparation and sequencingon the Illumina GAIIx, led to migration ofcancer services (BRCA, Lynch syndrome,FAP, Li Fraumeni syndrome,Phaeochromocytoma) to the Illuminaplatform and the first diagnostic NGS reportsin the UK. We subsequently introducedservices for paediatric-onset neurologicaland ocular disorders (optic atrophy, familialexudative vitreoretinopathy, cerebralmalformations), capitalising on local clinicaland research expertise. By the end of 2010,over two-thirds of our laboratory’s workloadutilised this approach.

PCR-based target enrichment has beenhighly successful at reducing hands-on andanalysis time,¹ and remains the cheapestand most efficient solution for targetsrequiring fewer than 20 long-rangeamplicons. In the hands of others, analogousmultiplex short PCR and digital PCRapproaches (Fluidigm, Raindance,Multiplicom etc.) have been similarly fruitful.

Figure 1: Illumina data handling and reporting pipeline.




24ACGS News

Targeted WES offers two considerableadvantages over clinical exome for suchdisorders. Firstly, the data can be re-analysedin future years in the light of newlycharacterised causative genes. Since the startof 2013, the number of causative PCD geneshas increased from 17 to 32, a rate ofdiscovery by no means unusual in thegenomic era, potentially rendering morespecific capture reagents obsolete as soon asthey are designed. An apparently costly wholeexome analysis can eventually lookinexpensive compared to repeat applicationsof an evolving targeted reagent over thecourse of several years! Secondly, with a largeproportion of the genetic component of manypaediatric constitutional disorders stillundiscovered, the data can be ‘sign-posted’(with appropriate consent) to specialistresearch groups for potential discovery of newcausative genes once the clinical gene panelis exhausted, offering families the maximumpossible clinical yield from one test.

The WES approach has been successful forPCD and Meckel/Joubert referrals; threenew presumptive PCD genes have beenidentified wholly or partially due to researchwork conducted on the diagnostic exomes3,4,5, two causative copy-number variationswere identified in the Translational GenomicsUnit, and overall diagnostic yield (see figure2) so far exceeds 40% for both services.

The Translational Genomics Unit in Leedshave also made some initial forays into thebrave new world of WES analysis for abroader range of mixed referrals, with thediagnostic laboratory confirming positivecases through our defined pipeline andproducing interpretive variant reports.

For further information on the diagnosticservices listed in table 1, please see ourwebsite http://www.leedsth.nhs.uk/a-z-of-services/molecular-genetics/ or contact usdirectly at [email protected].

4. Hjeij et al. (2014), CCDC151 mutationscause primary ciliary dyskinesia bydisruption of the outer dynein armdocking complex formation. Am J HumGenet. 95(3):257-74.

5. Watson et al (2014), LRRC56 is a novelgene causing primary ciliary dyskinesia(PCD) identified through exome baseddiagnostic testing. Poster P119, BSGMConference 2014

References:1. Morgan et al. (2010), Genetic diagnosis

of familial breast cancer using clonalsequencing. Hum Mutat. 31(4):484-91.

2. http://www.leedsth.nhs.uk/a-z-of-services/molecular-genetics/test-pages/cancer-chip-panel/

3. Watson et al. (2014), Robust diagnosticgenetic testing using solution captureenrichment and a novel variant-filteringinterface. Hum Mutat. (4):434-41.

Table 1: Paediatric and infantile-onset disease services offered in Leeds. The local areas of clinical and scientific expertise include paediatric neurology (particularlybrain malformation disorders), ophthalmological disease, and locally-prevalent rarerecessive neurological and developmental disorders, particularly ciliopathies. We also workclosely with the Leeds-based national Malignant Hyperthermia (MH) Unit to offer diagnosticMH screening. Developing areas of interest include neurological metabolic disorders (suchas cerebral creatine deficiency and leukodystrophy disorders). Services with an asterisk (*)have been approved for national provision by UKGTN.

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Figure 2: Diagnostic yields of targeted exome panels (including translationalresearch findings); 50% for Joubert/Meckel syndrome (JBTS/MKS) panel, 42% forprimary ciliary dyskinesia (PCD) panel.

“By the end of 2010, over two-thirds of ourlaboratory’s workload utilised [NGS]”




rate of genetic variation acrossarrhythmogenic disease and access towell phenotyped cohorts would beinvaluable. Until then, data interpretationand genetic counselling will remainchallenging.

The clinical side of these diseases wasexpertly covered; the problems ofdistinguishing between an athlete’s andan affected individual’s heart especially inethnic minorities in ARVC and thecardiomyopathies, problems with delayedresuscitation and new innovations inimplantable cardioverter-defibrillators(ICDs). It also transpires that two clinicalentities are no longer thought of ascausing pathogenic disease; EarlyRepolarisation Syndrome and Short QTsyndrome.

For those of you not fortunate enough toattend, the lectures are available viawww.cardiovascular-sciences.org. Therewas no charge for conference attendanceleaving hard pressed NHS trusts to covertravel and study leave only. This wasthanks to some very special sponsors:Boston Scientific, Biotronik, Aspetar,Virgin and the charity, Cardiac Risk in theYoung.

25ACGS News

ascertainment bias or genetic differencesremains to be seen. Dr Todd indicated inhis talk that the incidence of SCD barelyvaries with social economic status in theUK. However, in the USA there is amarked difference; with people of a lowsocio-economic status being significantlymore likely to suffer sudden cardiacdeath.

Professor Jacob Tfelft-Hansen outlinedan idea from Denmark: to make autopsymandatory in sudden cardiac deathcases. Cost is a major bar to theimplementation of this practice, eventhough family screening savings wouldmake this cost effective at a nationallevel. As Professor Arthur Wilde lateroutlined, family screening dramaticallyincreases the clinical sensitivity of geneticscreening and saves lives.

Lia Crotti, an internationally renownedexpert in the genetics of arrhythmogenicdisease discussed the genetic detectionrate in channelopathy genes. In particularthe recently associated CALM1, CALM2and CALM3 which are responsible for aclinical overlap syndrome of CPVT andLQTS with a severe young onsetpresentation. Professor Connie Bezzina,professor of molecular cardiogenetics,AMC outlined the problems associatedwith making a genetic diagnosis inBrugada Syndrome. Brugada Syndromeaccounts for about 4% of UK SCD cases.SCN5A is responsible for monogenicdisease in about 20% of cases, noBrugada causative genes have beenidentified by linkage and problems withlow penetrance, variable expression andnon-segregation make the elucidation ofthe remaining genetic componentsdifficult. Brugada Syndrome is nowmoving to an oligogenic model but moredata is needed to resolve the background

The beautiful Royal Institute of BritishArchitects building in London was thevenue of the 5th Annual CardiovascularSciences Research Centre meeting onFriday 28 November 2014. The focus ofthis meeting on sudden cardiac deathwas particularly relevant to the OxfordMedical Genetics laboratory as itlaunches a new arrhythmia panel,specifically aimed at individuals withnormal post mortem findings.

First of all we heard from Professor MaryShepherd, in charge of theCardiovascular Pathology Unit at StGeorge’s, University of London who hasestablished an international referral centrefor sudden cardiac deaths in the young.Mary gave us a detailed overview of thecauses of sudden cardiac death and howthese cases are managed. The ChiefCoroner, a legal position, is nowresponsible for referring all cases onto StGeorge’s.

Registration of sudden cardiac deathshas yet to be systematically carried out.This is another step towards changingthe handling of these cases andimproving survival rates. Families receivea detailed report of the findings within 14days of referral.

The unit is compliant with the HumanTissue Act and is capable of storing thespleen and heart when regional geneticslaboratory may not have the ability to doso. Autopsy budgets are astonishinglylow (just £97) meaning thathistopathology examinations and genetictesting has not previously been readilyavailable.

The incidence of sudden cardiac death(SCD) differs across international borders.Whether this is attributable to

Conference report: The A to Z of Sudden Cardiac DeathCaroline Sarton, Oxford Medical Genetics Laboratory.




benign to sudden death. As such diversepresentations can be seen within a family,molecular testing of ‘at-risk’ familymembers has far greater utility indetermining which relatives require life-long clinical screening and management.

The new cardiac arrhythmia geneticscreening panels have been designedwith careful consideration of the availableliterature and offer increased clinicalsensitivities compared to the previous fivegene screen for LQT and single genescreen for BS (see Table 1). The CPVTpanel is a new test to this department.The genes included on these three panelscome together to form a molecularautopsy panel of 33 genes, which wouldbe considered for Sudden Cardiac Death(SCD) individuals with no signs ofstructural heart disease. The laboratoryhas had success analysing DNA extractedfrom archived paraffin block samples,which opens up the possibility of genetictesting for ‘old’ cases. The technical basisfor this test is Agilent’s HaloPlex TargetEnrichment System combined withIllumina’s MiSeq Personal Sequencer andthis technique has been shown to workwith the small DNA fragments availablefrom paraffin blocks.

The laboratory uses a bespoke in-housepipeline, ‘HAPPy’, for data analysis whichallows greater flexibility for analysis ofalternative gene combinations such thatwe would welcome requests for othercombinations of genes from within thepanel of 33 genes for rare and unusualcases. The laboratory will continue tooffer screening by Sanger sequencing forTimothy syndrome, which includes thecommon variants responsible for classicand variant Timothy syndrome as well asthe newly discovered variant, c.3497T>Cp.(Ile1166Thr), in CACNA1C.2

26ACGS News

Cardiac Arrhythmia Multi GenePanels launched in OxfordCaroline Sarton and Karen McGuire, Oxford

in an autosomal dominant manner.Incomplete penetrance and variableexpressivity are key features of thesedisorders and the phenotype within asingle family can range from relatively

The Oxford Medical Genetics Laboratoryhas provided molecular genetic testing forcardiac arrhythmia for over ten years.During this time, it has seen its portfolio ofservices grow with advances inmethodology from screening of singlegenes through to the highly successfulfive gene screen. Now, the lab isdelighted to announce the launch of threenew, more comprehensive, cardiacarrhythmia services using massivelyparallel sequencing technology. Thistechnology has been part of routinepractice in this department since 2011and the cardiac arrhythmia panel followson from the large cardiomyopathy panelannounced last year.1

The term ‘cardiac arrhythmias’encapsulate a heterogeneous group ofdiseases that affect the electricalconductance of the heart, and arecharacterised by distinctive changes onelectrocardiogram (ECG):Catecholaminergic PolymorphicVentricular Tachycardia (CPVT) ischaracterised by adrenergically mediatedpolymorphic ventricular tachyarrhythmias;Long QT syndrome is characterised by aprolonged QT interval on ECG; andBrugada Syndrome (BS) is characterisedby ST-segment elevation on ECG,incomplete right bundle-branch block,and ventricular fibrillation (VF). Clinicaldifferentiation of these conditions can bedifficult, especially in atypical cases.Sometimes, these changes may onlybecome visible under specificenvironmental circumstances e.g. times ofstress (such as exercise, loud noises oremotional turmoil), during rest orpharmacological stimulation.

The arrhythmogenic disorders can beattributed to a monogenic cause in up to50% of cases, which are usually inherited

Gene Brugada Syndrome

CPVT Long QT syndrome

AKAP9 ! ANK2 ! CACNA1C ! ! CACNA2D1 ! CACNB2 ! CALM1 ! ! CALM2 ! ! CALM3 ! ! CASQ2 ! CAV3 ! DLG1 ! GPD1L ! HCN4 !! KCND3 ! KCNE1 ! KCNE2 ! KCNE3 ! KCNE1L (KCNE5) ! KCNH2 !!! KCNJ2 ! ! KCNJ5 ! KCNJ8 ! KCNQ1 !!! RYR2 !! SCN1B ! SCN2B ! SCN3B ! SCN4B ! SCN5A !!! !!! SLMAP ! SNTA1 ! TRDN ! TRPM4 ! Est. Clin. Sensitivity: 32-42% 50-65% 40-70% Price (UK & Ireland): £655 £655 £655 Price (Overseas) £786 £786 £786 Bespoke Test POA

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Table 1: Summary of Brugada syndrome,CPVT and Long QT syndrome panels.

� = Included in panel.

�� = Key domains guaranteed to becovered by >30 reads or by Sangersequencing.

�� = Coding region guaranteed to becovered by >30 reads or by Sangersequencing.




particular our presenters and forumfacilitators. I would also like to thank theACGS, especially the WDC, for all theirsupport in getting this day up and running– it is clear that it the event was very wellreceived and much appreciated by allwho attended.

Slides from the day will shortly beuploaded onto the ACGS website, as willa summary of the feedback anddiscussion forums.

27ACGS News

Genetic TechnologistTraining Day, Bristol20th November 2014Emma Clark, Sheffield Children's NHS Foundation Trust

Following a brief hiatus during which theACC and CMGS merged, a training dayfor technical staff working within geneticswas held last month. The event wasarranged via the Workforce DevelopmentCommittee and was supported by theACGS.

Over 80 people attended, with themajority of genetics labs and a variety oftechnical job roles being represented.

The morning consisted of introductorytalks on joining the ACGS andregistration, followed by discussionforums. Groups were split according towhat section they worked in and heldfocussed discussions on key points suchas training, registration and quality.

These forums also provided a chance todiscuss methods, kits and equipment withcolleagues from around the country. Theforums were lively and well engaged with,and were a great opportunity fornetworking.

In the afternoon session there was aseries presentations delivered by technicalstaff on a range of subjects across thewhole of the discipline. The talks werewell thought out and well delivered – Ihave since received feedbackcommenting on the high quality of thetalks.

Overall feedback from the day has beenvery positive, the day generated a lot ofinterest and enthusiasm from thetechnical staff and I am hopeful that wecan continue to hold such events infuture.

May I take this opportunity to once againthank all the attendees for their part inmaking the day such a success, in

Referrals for all of these services areaccepted from Clinical Geneticists,Cardiologists or other relevant medicalspecialists (in liaison with ClinicalGenetics). A fully interpretive clinical reportwill be issued within 60–80 days. Fasterturnaround times may be available incases of clinical urgency - please contactus directly. For further information, pleasevisit the laboratory website(http://www.ouh.nhs.uk/geneticslab) oruse the contacts below. Feedback fromservice users will be gratefully received.

Laboratory Contacts: Caroline Sarton Tel: 01865 225594. E-mail: [email protected] [email protected];

Karen McGuire, E-mail: [email protected]

Clinical Lead:Dr Edward Blair. Tel: 01865 225476. E-mail: [email protected]

References1. Hayesmoore, JBG (2014) BSGM

News, 50: 20-21

2. Boczek et al (2014) Heart Rhythm pii: S1547-5271(14)01076-5




seeking to increase the electronic traffic andsave trees, so please contact our LeadAdministrator, Christine Parkes, if you wish toreceive copies of our reports via nhs.net (viaour generic nhs.net e-mail account [email protected] alsoavailable on our websitewww.exeterlaboratory.com/molecular-genetics/).

28ACGS News

The postman never rings twiceCarolyn Tysoe, Andrew Parrish, Christine Parkes and Sian Ellard, Exeter

an internal relay system to which theStarLIMS system forwards the outgoingemails. This transfer is not encrypted, but isentirely contained within our local network,and the relay system then forwards theoutgoing emails to the intended recipient viathe NHS.net mail system. This transfer isobviously external to our trust, and istherefore encrypted using TLS authentication(naturally!). A really-good read produced bythe HSCIC called ‘NHSmail with applicationsV.7’ published in July 2013 details what anylocal IT department would need to gothrough in order to establish a similar localrelay for other StarLIMS users. In addition,there were a few local changes required toscripts within StarLIMS to set the emailoptions/content as we required. OurBioinformatics STP trainee Andrew Parrish([email protected]) would be happy togo through these in more detail with relevantpersonnel if any other laboratory usingStarLIMS requires assistance.

We have offered the option to receive reportselectronically to several referral centressystematically on a case-by-case basis overthe past 19 months and uptake has beenpositive with an average of 50% of reportscurrently being e-mailed (Figure 1). However,not satisfied with this, we are constantly

In 2006, a Devon postwoman was foundguilty of stealing more than 8,200 letters andparcels which were stored at her house overa period of six years. I can’t help thinkingthat this might be a common occurrenceunderlying the reason behind the number ofe-mail and telephone calls we receive fromclinical teams requesting copies of reportsthat were written and posted weeks, monthsand even years ago! In the modern digitalage is seems crazy not to adopt a moreefficient approach and to cease sendingsuch vitally important information via letterwith the associated risks of being stolen bypostpeople!

In Exeter, we operate a paperless LaboratoryInformation Management System (LIMS) sowe set out to facilitate the secure transfer ofclinically-actionable information in the form ofa clinical patient report using electronicmeans with the added benefits of providing aresult to the clinical team two to five daysfaster while saving on paper, postage andadministrators time. Following a period ofdevelopment with our LIMS provider,StarLIMS, we implemented a system tofacilitate the distribution of reports as pdf filesdirect to an nhs.net personal or genericaccount in April 2013. Here’s the cleverbit…briefly: our IT department have set up

Figure 1: Number of reports issued by e-mail (dark blue) as a percentage of totalreports issued (light blue)




candidates only wrote aboutbioinformatics tools OR databases, notboth, so lost marks.

4. Discuss the impact that nextgeneration sequencing will have onthe delivery of genetics servicesover the next five years. What arethe challenges and opportunitiesassociated with the introduction ofthis technology?

This question was answered by allcandidates sitting both exams. Thequestion was answered well and themajority of candidates achieved a passmark for this question. Lack of sufficienttechnical detail and failure to cover thechallenges associated with this technologywere the main reasons for failure.

5. What is the definition of a raredisease? Why is it important tohave a strategy for diagnosis andtreatment of rare disorders, and inwhat areas will genetic testingimpact on this strategy both nowand in the future? Illustrate youranswer with specific examples.

This question was only answered by twocandidates sitting the cytogenetics examand two candidates sitting the moleculargenetics exam. The question was notanswered well as candidates failed toaddress all parts of the question asked.

There were 24 candidates who sat thePart 1 practical examination in Autumn2014 - 10 candidates in clinicalcytogenetics and 14 candidates inmolecular genetics. The pass rate for bothexaminations was 100%.

29ACGS News

Feedback on the FRCPath Part 1examinations in Clinical Cytogeneticsand Molecular Genetics 2014Carolyn Campbell, Oxford University Hospitals NHS Trust, Stephanie Allen & Graham Fews, Birmingham Women’s NHS FoundationTrust, and Sally Cottrell, Great Ormond Street Hospital for Children NHS Foundation Trust

general was answered well. The mostcommon problems in failed essayquestions were insufficient factual detailand failure to answer all parts of thequestion.

2. The validation and verification ofmethods is a formal requirementfor accreditation according to thestandards applicable to genetictesting laboratories. Explain thedifference between validation andverification, giving examples ofhow you might go about each ofthese with respect to specificlaboratory testing protocols.

This question was answered by allcandidates sitting the cytogenetics examand 10 out of 12 candidates sitting themolecular genetics exam. Somecandidates lost marks because they didnot give examples, and some didn’tcorrectly explain the difference betweenvalidation and verification as requested. Inparticular, there was a lack ofunderstanding of verification and failure toprovide appropriate examples of theverification of protocols.

3. Bioinformatics tools and externalgenetic databases have becomeincreasingly important resources todiagnostic laboratories. Criticallyevaluate their use and limitationsillustrating your answer withexamples of each relevant toclinical cytogenetics and moleculargenetics.

This question was answered by 10 out of11 candidates sitting the cytogeneticsexam and all of the candidates sitting themolecular genetics exam. The mostcommon problems in failed essayquestions were focussing on a very limitednumber of databases and lack of detailrelating to limitations of their use. Some

There were 23 candidates who sat thePart 1 FRCPath written examination heldon 25th March 2014, 11 candidates satthe Part 1 written examination in clinicalcytogenetics and 12 candidates sat thePart 1 written examination in moleculargenetics. The pass rate for thecytogenetics exam was 73% and for themolecular genetics exam was 83%. Thiswas the second year that one of the essaypapers had been replaced by a paper ofshort answer questions (SAQs), and thisyear candidates sat the essay paper 1 inthe morning and the SAQ paper 2 in theafternoon. The SAQ paper consisted of 20SAQs to be attempted in 3 hours, whichapproximates to 9 minutes per question.Each SAQ has a stem and 6 sub-questions, is worth 20 marks in total, andis focused around a particular subject area(eg cystic fibrosis, array CGH, coloncancer, GWAS, chronic myeloidleukaemia). Time management appearedto have been less of a problem forcandidates with the SAQ paper this yearand the guidance given to candidatesrelating to how much detail is requiredwhen answering the questions wasfollowed by most. This year five of theSAQ questions were common to thecytogenetic and molecular papers, and forthe first time the essay paper was exactlythe same for the Cytogenetics andMolecular Genetics exams. The commentson the essay paper questions for bothdisciplines are summarised below:

1. Non-invasive prenatal testing(NIPT) for aneuploidy and non-invasive prenatal diagnosis (NIPD)for single gene disorders willrevolutionise prenatal screeningand diagnosis of geneticconditions. Discuss.

This question was answered by all of thecandidates sitting both exams, and in




30ACGS News

In remembrance of Dr Kevin OcraftNottingham Cytogenetics Department

from explaining a complex chromosomeabnormality, jump starting a car, resolvingthe latest IT frustrations to mending a bikepuncture late into the evening. All of thehelp was delivered with great patienceand good humour and this undoubtedlyensured that he fostered successful andproductive relationships with all that hecame into contact with. You could rely onKevin to show a friendly face with a bigsmile, he would always make time for youand had genuine concern for everyone’swelfare.

Messages sent to the departmentincluded time and time again phrases like“a lovely man”, “gentle“, “kind andgenerous”, ”professional”, “dedicated”,“caring”, “thoughtful”, “helpful”, “a realgentleman”... the list is endless.

In the wider profession, as many willknow, Kevin served for three years as thetreasurer of the ACC and latterly theACGS. His conscientious, diligent andknowledgeable approach to this rolehelped to ensure that this difficulttransition period was navigatedsuccessfully.

He was a keen cyclist and photographer.

He leaves behind his wife Susan andthree children Sarah, David and Lisa.

We miss Kevin being part of ourprofessional lives, but his legacy to thedepartment is that we continue to striveto deliver the best service possible, andkeep the patients as the centre of ourfocus.

Kevin sadly passed away suddenly onSaturday 24th May 2014. He worked inthe Cytogenetics Department inNottingham for 24 years, having earlierstudied for his PhD in Nottingham. Hehad worked in Tameside, St Mary’s andChristie Hospitals in Manchester beforegaining promotion to the post inNottingham. Whilst in Nottingham Kevinwas in charge of prenatal cytogeneticsand was latterly also deputy head ofdepartment. Kevin was the mostconsiderate, caring and supportivecolleague and boss and it was a privilegeto have worked with him for so long.

Kevin was very talented and we miss himprofessionally in so many ways, hisknowledge, his commitment to the serviceand his sheer hard work, but most of allwe miss the person that he was. Almosteveryone who came into contact withKevin would be struck at howextraordinarily helpful and kind he was.Assistance came in many forms ranging

CGG News Editors


Molecular Genetics EditorDr Martin J Schwarz PhD FRCPathRegional Molecular Genetics Service6th Floor, St Mary's HospitalOxford RoadManchester M13 9WLEmail: [email protected]: +44 (0) 161 701 4921Fax: +44 (0) 161 276 6606

Emma Huxley Clinical ScientistHaemato-Oncology sectionWest Midlands Regional GeneticsLaboratoryBirmingham Women's NHS FoundationTrust0121 627 [email protected]

Irene Carolina-GriffithsClinical ScientistReproductive Medicine sectionWest Midlands Regional GeneticsLaboratoryBirmingham Women's NHS FoundationTrust0121 627 [email protected]


discuss with applicants, and these will beavailable on the new GCRB website in thenear future. This development brings theboard into line with current practice inmost Higher Education Institutions. TheGCRB hope that use of this software willnot only reduce plagiarism in portfolios,but also improve the scholarly writingstyle of applicants.

Election of new GCRB membersGCRB elections for new board memberstook place in September, and as a resultCaroline Kirwan, Vishakha Tripathi andMelanie Watson will take up their placeson the board in January 2015. The GCRBwould like to thank Lorna McLeish,Barbara Stayner and Sally Watts who arestepping down, having now completedtheir tenure. Barbara, Lorna and Sallyhave all made important contributions tothe work of the GCRB.

Sign-off Mentor (SOM) trainingSOM training is arranged annually, andthe next course will be in Glasgow on 10June 2015 after the ESHG conference. AllSOMs should attend a training courseevery 3 years, so remember to planahead and ensure that departments havesufficient trained SOMs to support geneticcounsellors going through registration.Please contact the GCRB administratorChris Barnes if you would like to book aplace on the course.

GCRB Annual General Meeting (AGM)The AGM will be on 8 June 2015 at 12.30at ESHG conference in Glasgow. All arewelcome to attend.

New registered genetic counsellorsCongratulations to the following geneticcounsellors registered with the GCRB inJuly 2014.

31AGNC News

Editorial

Accredited Voluntary Registration (AVR)Recently the GCRB asked eachRegistered Genetic Counsellor if theysupport the GCRB in submitting anapplication for Accredited VoluntaryRegistration (AVR) to the ProfessionalStandards Authority (PSA). The result ofthe anonymised poll, coordinated by ouradministrator Chris Barnes, showedoverwhelming support for AVR.

Votes were received from 106 registeredgenetic counsellors (57% of the 186currently registered).

• YES: n=102 (96% of votes cast)• NO: n= 3 (3% of votes cast)

(In addition, one vote was declared invalidas a non-valid registration number wasgiven.)

With this strong mandate the JointCommittee on Genetic CounsellorRegulation (JCGCR) and the GCRB willnow finalise the application, which will besubmitted by the end of 2014.

GCRB websiteThe application for AVR will bestrengthened by the new GCRB website,which will be launched in the near future,and will include an online facility forpayment of fees for GCRB registrationand renewal of registration. We willinform all genetic counsellors when thewebsite is in action.

GCRB registration and plagiarismsoftwareThe use of plagiarism software is beingintroduced to the registration processfrom 2015. The documents for using theiThenticate plagiarism software(http://www.ithenticate.com/) have beensent to all Sign-off mentors (SOMs) to

Whilst reading through the articles for thisissue, I was struck by just how much thefield of genomics is becoming areoccurring theme. It seems that the wordgenomics is becoming more integratedinto our vocabulary, and it looks like it willbecome increasingly assimilated in ourroles as genetic counsellors, whether in aclinical or research setting.

This issues AGNC report outlines someexciting new proposals for the future,which embraces our role in genomicseducation. We also have reports from twoconferences from our well-travelledcolleagues, and in amongst theprogramme highlights are presentationson genomics and our role in patient care.

It really is quite a packed section for theAGNC this issue. We have an updatefrom the registration board, outlining theresult of the Accredited VoluntaryRegistration vote, for which the vastmajority are in favour. The opinion piecetakes a look at the impact of the wealth ofinformation that patients have access tobefore even seeing us in clinic, and thechallenges and benefits that brings. Thereis a genetic counsellor training panelupdate, as well as results from the surveylooking at the roles of genetic counsellorsand nurses in inherited cardiac conditions.I would also like to draw your attention tonew publications for parents and patientswith sex trisomies that have beendeveloped, and are available from Unique.

Happy reading!

Judith Edhouse

Genetic CounsellorRegistration Board(GCRB) update Diana Scotcher (Manchester) and Barbara Stayner (Oxford), Co-Chairs GCRB


32AGNC News

Jessica Bailey Emily Clarke Andrea Edwards Claire Giffney Sasha Henriques Jessica Hensman Lisa Hughes Kelly LoggenbergJessica Myring Elizabeth Ormondroyd Joanna Patterson Nicola Taverner

Contact the GCRBPlease contact the GCRB through theAdministrator Chris Barnes [email protected] if you haveany queries relating to registration or thework of the GCRB.

cancer and general genetic counselling,and research. Around two thirds of allrespondents would appreciate training incardiology, while three quarters of nurserespondents would appreciate training ingenetics. Counselling training was alsoendorsed. Respondents elaborated in freetext comments that issues specific toICCs in cardiology, genetics andcounselling were important.

We welcome hearing from interestedpeople to form a working party to thinkabout how training might beimplemented. Please contact: LizOrmondroyd([email protected]) or KathAshcroft ([email protected])

Reference1. http://www.england.nhs.uk/wp-

content/uploads/2013/06/a09-cardi-inheri-card-con.pdf(accessed 1.12.14)

Association of InheritedCardiac Conditions(AICC) surveyLiz Ormondroyd (Oxford) and Kath Ashcroft (Leeds)

Inherited Cardiac Conditions (ICCs) are agroup of largely monogenic disordersaffecting the heart, its conducting systemand vasculature. The first indication issometimes sudden cardiac death (SCD)often in adolescents or early adulthood. AService Specification for Inherited CardiacConditions, including arrhythmiasyndromes, cardiomyopathies, inheritedarteriopathies, muscular dystrophies andfamilies afflicted by Sudden ArrhythmicDeath Syndrome (SADS) was recentlypublished by NHS England1. The statedaim of ICC services is to improve thediagnosis, treatment and outcome ofpatients with inherited cardiac conditions,and achieving this aim requires specialistclinical management by multidisciplinaryteams including:

“Genetic Counsellors to provide pre- andpost- test counselling and to co-ordinateDNA testing, aid in genetic datainterpretation and cascade testing of at-risk family members. ICC nurse specialistswith training in counselling, and in theevaluation and management of adults andchildren with inherited cardiovascularconditions”.

Since little is known about theemployment of genetic counsellors andspecialist nurses with ICC services, weundertook a survey on behalf of the AICCto learn who is doing what, and whatadditional training they considerappropriate.

68 respondents from across the UKcompleted a ten item survey; 40% weregenetic counsellors, and 60% wereregistered nurses. The registered nurseswere especially diverse in terms ofbackground, qualification and roles withinservices. In addition to working in ICC,many genetic counsellors also carry out


antenatal treatment of Down syndrome,describing how early diagnosis of Downsyndrome using Non-Invasive PrenatalTesting (NIPT) could present a window fortreatment of the condition. This talk haschanged the way I now think about NIPT,highlighting that in genetics you can neverstop revisiting the basic understanding ofa topic.

The Sunday educational session:Responding to guilt and shame in clinicalconsultations was a particular highlight ofmine. During this session Clare Baguley,from the UK Psychological ProfessionsNetwork, addressed what we know aboutthese fundamental human emotions. Shedescribed the normal process ofadjustment to new information whichaffects life decisions, and highlighted howthis can become dysfunctional in somepeople. We watched a powerful role playof a clinic situation which demonstratedhow acknowledging and attending tothese feelings in a counselling sessioncan help the patient share their feelingswhich can inform the rest of the session.

So, whilst waiting in the airport for myflight home I found myself reflecting onthis trip of many firsts. I was leftexhausted but overall enthused by thiscommunity I am now part of. I couldn’thelp feeling that although medicalgenetics is facing new and excitingchallenges, it has been facing similardebates in different guises since theprofession was born.

I would like to thank the AGNC for thesupport to attend and present at thisconference.

33AGNC News

European Human Genetics Conference(ESHG) and European Meeting onPsychological Aspects of Genetics (EMPAG)June 2014, Milan: meeting reportElizabeth Alexander (Manchester Centre for Genomic Medicine)

Nevertheless, as a new genetic counsellorI am acutely aware that I am currentlydeveloping my basic skills of geneticcounselling. The big questions on newtechnologies and the excitingopportunities they bring, for me at presentit is a backdrop rather than the focus ofmy career. Even from this standpointthere was much to adsorb from EMPAG.Speakers addressed the language we usewith patients, how to communicate risk,how to support our patients with geneticknowledge, decision making, and how todefine a child’s right to an open future.These fundamental questions are nowbeing debated anew in the face of thenew technologies.

The Saturday plenary session onreproductive decision making highlightedthis point. In particular the sessions ondecisions around screening for Downsyndrome in pregnancy given by Marcia LVan Riper (USA), and CharlottaIngvoldstad (Sweden). As one of the firstconditions identified as having a geneticbasis and tested for prenatally since thesixties, one would assume that this was awell-developed area. Van Riper andIngvoldstad’s work showed this is notuniformly the case, and there is still aneed to educate around providing parentswith pre-test information on Downsyndrome to enable informed prenataldecision making.

This begs the question; if this informationand education aren’t delivered well, whathope do we have as new technologiesmove in? This reminded me howimportant it is not to leave the basicsbehind as we move into this new era. Athought emphasised by one of the mostenlightening talks I attended. D.WBianchi’s presentation Non-invasiveprenatal testing creates an opportunity for

As newly qualified genetic counsellor thiswas a trip of many firsts; my firstconference as a genetic counsellor, myfirst EMPAG, and my first time co-presenting my qualitative research project.

When starting a four day conference it isimpossible to imagine that I could sustainattending all of the sessions, but whenlooking through the EMPAG programme,it was hard to imagine what I could miss.Whilst many of the sessions evoked thetraditional values of genetic counselling, acloser look at the talks left no doubt thatthe new era of genomic medicine ranthrough the whole programme. Many ofthe talks addressed the complexities ofoffering whole genome sequencing, whatto do about incidental findings and howto present and consent our patients tothese tests. It is reassuring to see theinternational community experiencing thesame dilemmas, and learning from eachother how to approach these issues.

Enjoying the sites of Milan, during a well-earned break: (from L-R) Kate Brunstrom,Sarah Bennett, Theo Gale, ElizabethAlexander, Lyndon Gallacher, DebbieHolliday, Sian Jenkins and Helen Jolley


34AGNC News

Challenges and benefits ofincreasing public genetic awarenessEmma Williams (NE Thames)

As genetic counsellors, our profession isperhaps one that the general public, and tosome extent other clinicians, are lessfamiliar with. As a result of this, part of ourrole has always involved education aboutwhat genetic counselling is, to not only ourpatients but also other health professionals.

Over the last 18 months we haveexperienced a significant increase in thenumber of women seeking geneticcounselling and gene testing. This waslargely following the press coverage aboutAngelina Jolie undergoing risk-reducingbreast surgery, following identification of herBRCA carrier status, which generatedmuch international attention. The updatedNICE guidelines in 2013 also included theoption for unaffected BRCA testing incertain circumstances.

Increasing awareness is hugely important,especially in the field of cancer genetics,where there are options available for cancerrisk reduction or early detection. While ourcancer genetics team has seen at least atwo-fold increase in referral rates, since thesummer of 2013, we observed that themajority of this increase has been forwomen who would not be considered tobe at high risk on the basis of their familyhistory, so consequently would not meetthe referral criteria for an appointment inthe cancer genetics clinic, let alone aBRCA1/2 gene test on the NHS.

Of those who have been offered anappointment in clinic, we have noticed thatan increasing number of patients attendwith the opinion that they have obtainedsufficient knowledge and understandingabout the BRCA genes and gene testingprior to the appointment, and view geneticcounselling as a gate-keeping process fortesting.

much as possible. This is particularlyimportant as recent developments insequencing technology and the decreasingcost of testing, mean the complexity ofgenetic information that is available topatients is almost certain to increase in thenear future.

With the internet and social media being aprimary source of information for a growingproportion of our population, this is hardlysurprising. However there is such a breadthof unmonitored information that is readilyavailable on the internet, and also frompeers through online supportgroups/forums, my concern would be thatpatients sources of information may notalways be that accurate and reliable.

It has been my experience that this has ledto a number of more challenging geneticcounselling consultations, when a patientwho considers themselves to be welleducated about the genetics of breastcancer, has actually been misinformed ormisunderstood the nature of anappointment in a cancer genetics clinic orBRCA gene testing.

As an experienced cancer geneticscounsellor, I am used to explaining thereasons behind a decision not to offer genetesting to an unaffected patient when theydo not fulfill the criteria, and explain thecomplexity and possible limitations ofinterpreting a BRCA testing in unaffectedpatients.

I have more recently encountered a smallminority of patients who are certain thatthey are entitled to a gene test, irrespectiveof my explanations, the belief of which mayhave been initiated by a referring clinician.Managing these expectations can be verydifficult.

I would imagine that this type of experienceis not unique to our department, and thatother genetic counsellors throughout theUK may be facing similar challenges. I thinkit highlights how important it is that wecontinue with our role as educators to bothpatients and clinicians to try and alignexpectations with what we can offer as


discussed how nurses could participate aspart of larger interdisciplinary researchprogrammes, and were needed to retainfocus on the patient and the family.

Choosing just one of three concurrentsessions to attend over the next couple ofdays proved difficult. I found Case studiesto enhance education, most inspiring. HereKathleen Calzone presented the GlobalGenetics and Genomics Community(http://g-3-c.org/en) use of on-linesimulations for teaching. This demonstratedto me how far US teaching resources havedeveloped over the last few years. MaggieKirk showed videos of the genomicsteaching at the University of South Walesand their pioneer use of drama, wherestudents act out characters in an unfoldingstory. Concurrently more traditionalconcepts such as culture and genetictesting were an option, with presentationsfrom Israel, Columbia and Brazil.

On the second day I attended the sessionsrelating to genomics education. KarenWhitt and Delwin Jacoby both presentedon-line courses they had developed attheir own Universities to integrate geneticsand genomic teaching into the nursing andallied health professional curriculum.Others presented the development of

35AGNC News

Conference report: The International Society ofNurses in Genetics (ISONG) World Congresson Nursing and Genomics, November 7th-9th2014, Scottsdale, Arizona, USACaroline Benjamin (School of Health, University of Central Lancashire)

Nursing Research development of the2013 Blueprint for Genomic NursingSciencewww.ninr.nih.gov/genomicsblueprint. Thisexplores ways to further genomic nursingscience to improve health outcomes forpatients. It also provides grant funding fornurses wishing to conduct genetic orgenomic research. She stressed that,“nurses are with the patient and familyduring and after genetic information isshared”. Many nurses in the US areinvolved in translational research projectsranging from biological laboratory sciencethrough to psychosocial genetic andgenomic issues. Her own work focuses ondetermining if there is an inheritedpredisposition to Irritable Bowel Syndrome.

A symposium later that day focused onJump Starting your Career in Genetics as aNurse Scientist, with presentations fromTaura Barr and Jacquelyn Taylor. Both arenurses running their own laboratoryresearch into diseases such ashypertension, stroke and symptomcharacterisation. Other presenters

Scottsdale is located in the Salt RiverValley, also known as the ‘Valley of theSun’. During my stay it lived up to its namewith average daytime temperatures of 26C.

I have been involved with ISONG for anumber of years and the UK hasdemonstrated international leadership withpast presidents including ProfessorHeather Skirton and Professor Maggie Kirk.

I was fortunate to be an invited sessionspeaker to present The scoop on ourscope; what’s new with the scope ofpractice for genetics nursing, and alsodelivered a research abstract presentationInterdisciplinary working, workforceutilization and referral management: resultsof a prospective study. The meeting wasattended by 250 registrants, representingten countries. It consisted mainly of nursespractising as advanced practice geneticnurses (APGNs), nurse educators andresearchers. A diverse programmeincluded 82 spoken sessions and 25posters.

The first day’s keynote was delivered byMargaret Heitkemper, Professor of Nursingat the University of Washington. Shedescribed the US National Institutes for

Caroline getting to know the locals,Scotsdale, Arizona.

Susan Wesmiller, Assistant Professor, HealthPromotion and Development, University ofPittsburgh presenting an ISONG ResearchGrant to Caroline Benjamin.

Downtown Scottsdale


36AGNC News

instruments to measure genetic literacyprior to and after educational interventions,such as the Genomic Nursing ConceptInventory (Linda Ward).

The Genomics in Practice sessions overthe two days concentrated on clinicalpractice settings such as perinatal, cancergenetics and genomics and chronicdisease. There was an excellentpresentations by patient support groupFORCE (Facing Our Risk of CancerTogether)(http://www.facingourrisk.org/index.php)showing the benefit of this informationsource for patients. Also the developmentof an App to increase BRCA providerknowledge at point of care.

The ethical, legal and social issue keynotewas presented by Malia Villegas, Directorof the National Congress of AmericanIndians. This was enlightening regardingthe involvement of these groups inhistorical and ongoing bio banks, includinggenetics research. She explained how thesaying “walk softly, listen carefully” guidedtheir work in facilitating an understandingof cultural issues between researchers andparticipants.

The full programme and details of theorganisation is available fromhttp://www.isong.org . I would encourageUK nurses, counsellors and thoseinterested in clinical practice, education orresearch to consider joining thisinternational organisation or attend theCongress in Pittsburgh next year. Itprovides opportunities for education,research collaboration and professionaldevelopment.

I would like to thank the AGNC forproviding a travel grant, which enabled meto attend this meeting.

Since the 100,000 Genomes project wasannounced in 2012, the clinical geneticscommunity has been awaiting details ofhow we will be involved in this mostambitious government initiative. 2014 hasseen Genomics England Limited (GeL), theDepartment of Health-owned companyresponsible for delivering the project,stage a series of events and presentationsaround the country aimed at educatinghealth professionals and the public alikeabout the potentially very exciting legacyfor genomic healthcare in the UK.

Committee and other members of theAGNC have been lobbying GeLthroughout 2014 to promote geneticcounsellors as versatile clinicians uniquelyplaced in the NHS not only to help recruitpatients into the project and providespecialist care to those families impactedupon by findings but also to assist intraining the mainstream workforce inaspects of genomic medicine. The AGNCvision statement, available on our website

and discussed in the last newsletter, wascertainly developed with this in mind.

We have also been liaising with HealthEducation England, which will be co-ordinating workforce training and planningin anticipation of 100,000 Genomes. As aresult of this engagement, together withrepresentatives from the GeneticCounsellor Registration Board (GCRB),Joint Committee on Genetic CounsellorRegulation (JCGCR), lead geneticcounsellors, and the Genetic CounsellorTraining Panel (GCTP), an opportunity totransform genetic counsellor training andfunding has been presented. Discussionsabout this are at a very early stage butone possible option being considered isan intercalated, funded, MSc and trainingpost scheme along the lines of the NHSScientist Training Programme. Clearly, thiswould be a major change from the currenttraining routes and any forthcoming detailswill be carefully scrutinised in the interestsof our profession.

AGNC report, Winter 2014Peter Marks, AGNC secretary (Birmingham)

The AGNC committee November 2013: (from L-R) Liwsi-Kim Protheroe-Davies (Swansea),front- Cath King (Bath), back- Anita Bruce (GOSH), Oonagh Claber (Newcastle), PeterMarks (Birmingham), Claire Giffney (Birmingham), Laura Boyes (Birmingham).


37AGNC News

In anticipation of our likely role ingenomics education of the mainstreamworkforce, the committee is stronglycommitted to promoting the up skilling ofUK genetic counsellors in the fields ofgenomics and bioinformatics. Theforthcoming ESHG meeting in Glasgow inthe spring of 2015 will feature a numberof key sessions around these subjects,and the AGNC committee has decided tooffer funding grants enabling one memberfrom each genetics centre to attend thismeeting. It is expected that the leadgenetic counsellor from each centre willsubmit an application on behalf of theirnominated genetic counsellor. TheWellcome Trust Genomic Counselling forGenetic Counsellors course in July 2015at Hinxton, will also help to ensure thatgenetic counsellors are prepared foradvances in the field of genomics.

In other news, the committee iscontinuing its work into sharing geneticcounsellor practice nationally and will beconducting a pilot survey of practicearound predictive testing for adult onsetconditions for which treatment and/orsurveillance is available. It is anticipatedthat surveys will be completed by the leadgenetic counsellor from every geneticscentre in the UK in order to provide asnapshot of current practice. The findingswill be published by the committee in thesummer of 2015.

We would like to thank Oonagh Claberand Cath King for their terms serving onthe committee. Oonagh recently servedas secretary and Cath as treasurer. Theirhard work has been much appreciated.We now welcome their successors on thecommittee, Pam Harris and AnnaMiddleton. We also say thank you andgoodbye to Claire Giffney, who hascompleted her term as the new geneticcounsellor representative and who is

succeeded by Helen Jolley. We welcomeHelen and look forward to working withher.

Finally, I would like to take this opportunityto remind all members that AGNCmembership is free for student geneticcounsellors (though a discounted BSGMannual subscription – currently £20 – isrequired). Do encourage students basedin your centres to join so that they cantake advantage of the benefits of being amember, be represented, and bewelcomed into a professional communityof which they will soon be part.


• Not all participants were members ofthe AGNC. Membership of the AGNCis actively encouraged as a way ofmaintaining currency with professionalissues, supporting best practice anddelivering high quality patient care.

• The training day was a success andprovided participants with a forum tonetwork, gain peer support and sharegood practice. Participants appearedto particularly value the opportunity todiscuss and present cases and toshare experiences with their peers.Participants’ commitment tostructured, competency based trainingand their desire to share evidencebased practice was particularlyimpressive.

• In light of the positive feedbackreceived, the GCTP plans to organiseanother training day in 2015. If it is felthelpful, this could include participationfrom training mentors.

Training panel members

Judy Tocher (Chair)[email protected]

Claire [email protected]

Sue [email protected]

Rhona [email protected]

With thanks to: Claire Giffney, AGNC newgenetic counsellor representative, andAntoniya Ruseva, genetic counsellortrainee

38AGNC News

Genetic counsellor trainee meeting25th June 2014Claire Dolling (Birmingham)

and a presentation on teaching genetics.There was opportunity for small andwhole group discussion and casepresentations. Feedback from the daywas extremely positive with participantsappreciating the opportunity to networkand share their training experiences. Thecase presentations and subsequentdiscussions appeared to be particularlyvalued, and provided an opportunity toshare good practice.

Genetic counsellor trainees: update • Departments appear committed to

genetic counsellor training, and aresupporting this in a variety of ways.Centralised funding would ensure thatthis is sustainable and help maintain ahigh standard of training. The AGNC isactively working towards this end.

• The day highlighted the benefits of alearning contract, which is based onregistration competencies and isregularly reviewed. The learningcontract provides a structured tool toidentify an individual trainee‘s learningneeds and help monitor progress. TheGCTP actively encourages the use oflearning contracts for all new geneticcounsellors and is happy to reviewlearning contracts and offer guidancewhere needed. Information on learningcontracts is available in the GCTPsection of the AGNC website(www.agnc.org.uk)

• Current new recruits have mainlyentered the profession via a scientificbackground plus MSc in geneticcounselling route. We need toconsider ways to support andencourage applicants with nursingbackgrounds in order to maintain thediversity that nurses and midwivesbring to the profession.

Genetic Counsellor TrainingThere are currently two entry routes tobecome a registered genetic counsellor inthe UK:

• Registered nurse or midwife with atleast two years post registrationexperience and additional counsellingand genetics training.

• Graduate from one of the two UKbased MSc Genetic Counsellingprogrammes, accredited by both theUK Genetic Counsellor RegistrationBoard (GCRB) and the EuropeanBoard of Medical Genetics (EBMG).

Two years of supervised clinical trainingthen provides sufficient experience to fulfilcompetencies for genetic counsellorregistration. Following the 2003(Department of Health) DH white paper,“Our Inheritance, Our Future” the DHprovided funding for 50 trainee geneticcounsellor posts. This centralised fundinghas now ceased, with reliance instead ondepartmental budgets to fund this trainingperiod.

The AGNC is actively pursuing options tosecure centralised funding for future highquality genetic counsellor training, in theUK. Meanwhile, the Genetic CounsellorTraining Panel (GCTP) continues tofacilitate and monitor posts aimed attraining genetic counsellors for registrationin the UK and Republic of Ireland.

On 25 June 2014, the GCTP organised aGenetic Counsellor Trainee meeting atBirmingham Women’s Hospital. Twentyone trainee genetic counsellors attendedfrom England (16), Scotland (4) and Wales(1). The programme included spokenpresentations addressing professionalissues such as registration and training,


Reference1. The manuscript about current

disclosure choices (Gratton, Myring,Middlemiss, Shears, Wellesley, Wynn,Bishop and Scerif, under review) isavailable upon request (please emailGaia Scerif, [email protected]).

39AGNC News

Children with sex chromosometrisomies: booklets to help parentstell their child about a diagnosisSarah Wynn (Unique, Rare Chromosome Disorder Support Group, Oxted, Surrey), Dorothy Bishop and Gaia Scerif (Department ofExperimental Psychology, University of Oxford)

The booklets were designed after surveyingparents to find out more about factorsaffecting a decision to disclose a diagnosis,and ways in which parents had gone aboutthis. The researchers also asked for theviews of young people who had 47,XXX or47,XYY who knew about their diagnosis.

The goal was to produce, for eachcondition, two booklets. The first one is forparents, and discusses the pros and consof disclosing the diagnosis. The aim is togive parents information that will help thembalance different factors in coming to adecision. For instance, many parents wereconcerned that if they disclosed thediagnosis, then this could lead to the childbeing stigmatised. On the other hand, thechild might be relieved to have a diagnosis,particularly if it provided an explanation fordevelopmental difficulties.

To help those parents who decide todisclose the diagnosis, the researchersdeveloped a picture book for eachcondition. This is suitable for children with adevelopmental level of around 6 to 10years. It does not explain complexgenetics, but focuses on the idea thathaving an extra chromosome is just oneway in which people can be different fromone another. It is hoped that if parentsstart this conversation with the child whenthey are fairly young, they can then allowunderstanding to develop more graduallyas their ability increases with age.

Printed copies of the booklets for parentsand children are available from Unique(please email Sarah Wynn,[email protected]), and the bookletscan also be freely downloaded from theweb (www.rarechromo.org or onhttp://dx.doi.org/10.6084/m9.figshare.1203560).

When a child is diagnosed with achromosome disorder, parents will want toknow what the impact will be for the childand the family. Another question that willarise sooner or later is how to discuss thediagnosis with the child and with otherpeople. If the disorder has obvious effectson development, then a diagnosis can behelpful in providing an explanation. Thingsare more complicated, though, for acondition such as a sex chromosometrisomy (47,XYY, 47,XXX also known astriple X or trisomy X, and 47,XXY, alsoknown as Klinefelter's syndrome). Childrenwith all three trisomies are at risk ofeducational difficulties, particularly thoseaffecting language and communication, butthe range of outcomes is very wide. Mostchildren attend mainstream school andsome will go on to university.

Many parents are concerned aboutwhether or not to tell their child about thetrisomy. For example, a team ofpsychologists, clinical geneticists, geneticscounsellors and members of Unique foundthat parents of children with a sex trisomywere less likely to disclose to their child,siblings and school if their child had highercognitive, social and emotional functioning1.Those parents who wanted to tell theirchild also reported that they felt unsureabout how to go about doing this.

With funding from the Nuffield Foundation,researchers at the University of Oxford havedeveloped a set of booklets designed tohelp parents confronted with this issue.They focused on 47, XXX and 47, XYY,because in these conditions there is nogood evidence of any effect on sexualdevelopment or ability to have children. Theissues are more complex in Klinefelter'ssyndrome, where there are effects onpuberty and fertility.

AGNC News Editor


Judith EdhouseRegistered Genetic Counsellor, no. 243

Department of Clinical GeneticsWard 10, 3rd FloorChapel Allerton HospitalLeeds Teaching Hospitals LS7 4SA

Tel: 0113 392 4407Fax: 0113 392 4434Email: [email protected]


Change is in the air and don’t we know it.Many of you will be suffering from ‘tenderfatigue’ following a busy few months ofdrafting, site visits and rearrangingeverything at the last minute to attendmeetings. There are so many initiativesunderway that it’s becoming difficult toimagine just what the role of today’sclinical geneticist will be in the futurehealth service. The Lead Clinicians andCGS council met to debate this justrecently and sought advice, too, fromother specialties of what exactly theywould want from us in years to come. Weare writing a summary of the fullproceedings of that meeting which will beavailable to everyone in due course.Those who have been pondering justwhat you will be doing in a couple ofyears, however, might be interested in asnapshot of the views of our mainstreamcolleagues from cardiology, oncology andgeneral practice, all of which provokedsome interesting discussion.

Our trainees were particularly worriedabout the change we will have to makefrom Clinical Geneticists to ClinicalGenomicists. It had been remarked byothers outside our specialty that that thisconjured up a workforce of small peoplein red hats, not an image we would like toproject. But it turns out not to be a majorworry, as the mainstreamers we askedcertainly didn’t think we would all have‘Gone fishing’.

Many mainstream specialities are alreadyconversant with genomics and use it intheir everyday practice. They felt that withresults from the UK 100,000 genomestudy coming through, with new genomicdiscoveries which could influencetherapies, and with a new generation oftrainees who will be more genomicsliterate, that they envisage a world where

40CGS News

Letter fromthe President: The times theyare a-changingProfessor Jill Clayton-Smith

EditorialDerek Lim

One of the broadening roles of the CGS isto foster international relationships withother genetics centres. One of the waysthis is achieved is through the CGSInternational Scholarship. Dr Neerja Guptafrom New Delhi was awarded thescholarship in 2013 and we hear about DrGupta’s experience in Manchester.

Please remember to keep the date 3March 2015 in your diary for theupcoming CGS spring conference inLondon at the Royal College ofPhysicians. I hope that theregistrars/trainees have taken theopportunity to submit an abstract for theRobin Winter SpR Prize and judging bythe quality of the presentations in previousyears, I am confident that the standardswill remain high this year. The traineereport in this edition also highlights thevarious funding opportunities provided bythe CGS and I encourage you to takeadvantage of this.

Finally, we are very sad to lose acolleague in Birmingham and we featurean obituary on Dr Louise Brueton. On apersonal note, I am very proud to havetrained under Louise and am very gratefulfor the guidance and support she hasgiven me throughout my career ingenetics. This paragraph was particularlydifficult for me to compose without feelingupset but that just goes to show thelasting impact she has on the people shemet and the patients she cared for asevident by the tears shed and the verykind words about Louise relayed by herpatients who I’ve met in clinic wheninformed about her passing. At difficultand sad times like this, we often thinkabout our close family and friends but Iwould add that we not forget ourcolleagues around us.#LifeIsShortAndPrecious

Derek Lim

Welcome to the latest edition of the CGSsection of BSGM news. What a busy time ithas been for all of us in clinical genetics notonly in terms of the clinical workload but a lotof us would have also been involved withvarious aspects of engaging with the 100KGenomes project and the tight deadlines. It isan exciting time to look ahead as we move into the genomic medicine era. Mainstreaminggenetics continues to be on the agenda aswell and our president discusses importantaspects of our future roles in clinicalgenetics/genomics. The times are a changingindeed. I couldn’t help but create a littlecartoon to accompany Jill’s letter because ofthe image that she has conjured up (read onfor further details) in my mind.

Many of us would have met or heardWendy Jones, a clinical PhD studentworking at the Wellcome Trust SangerInstitute, present her research and herinvolvement with the DDD project. Wendyhas kindly contributed an article abouttips and guidance about choosing a PhDproject as well as the importance ofclinical geneticists to learn to programmeto interrogate the big data that we will nodoubt receive in the near future. Yes wewill have bioinformaticians, but having thatadded knowledge to our repertoire ofskills will be very beneficial.

I am pleased that Mary O’Driscoll agreedto review a selection of available apps forsmartphones and tablets that are relevantto genetics including the TGCA app thatwas developed by some of our membersat St George’s Hospital. We shouldembrace the technological advancementsin such handheld devices and take theopportunity to utilise them for patientbenefit. Instant knowledge accessible atyour fingertip is very powerful. Speakingfrom personal experience, sometimes, itcan even save you from embarrassmentin an MDT meeting when inflicted with thedreaded brain-freeze moment.


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was interesting for us to realise that GPsfeel they only have time to learn what isrelevant to the case in hand and so notmany are likely to opt to go on courses orattend lectures in genomics, as it may besome time before they see a patient witha genomic disorder. Their challenge ishow to maintain their generalist and careco-ordinator role whilst learning aboutnew things like genomics. As far asgenomics goes, when the situationpresents, they want the resources at handto be able to address this and we sawinteresting demonstrations of systemswhich allowed temporary sharing ofelectronic clinical records to get advicefrom specialists and links directly from theGP desktop to pathways for testing andcounselling for example inhaemachromatosis. Those who havebeen sceptical about genomic medicinecoming to GP-land are undoubtedlywrong. Whilst they would still like us tosee complex or rare disease patients theydon’t see that all of their patients need tobe seen face to face and want to speedthings up for them by interfacing betterwith us, with most of this interfacing beingdone electronically. When we do sendletters, they would like these to clearlystate a problem list and an action plan sothat these key features can be entered asfields onto the GP database rather thanless structured letters simply beingscanned in.

It’s clear that as a specialty we need tolead change in this genomics era. There isno room for us to be precious; we have tomake ourselves useful to other specialtiesas they evolve. The message is that weare “Better together” and we need toheed the request for subspecialisation.We discussed models such as Post-CCTfellowships for mainstream and genomicstrainees to become conversant with eachother’s specialties and support fordevelopment of genetic counsellors inspecialist areas. Within our owncommunity, clinicians, counsellors andscientists need to deliver genomicstogether. There will be some other keyrequirements for our evolving role; accessto training in new skills such asbioinformatics for existing consultants, notjust for trainees, and importantly, a keyneed to address the IT deficiencies withinour Trusts. Commissioning too will needto address new models where not everypatient is seen face to face.

So, trainees, I have done it. I havechanged us from geneticists togenomicists within the course of this shortarticle. And in my head, I have changedus from the small men with red hats tosomething more akin to the little stickman with a reputation for helping that Iused to have on my Brownie uniform.Brown Owl knew something all thoseyears ago when she put me in theg(e)nomes.

much genomic advice would be given bythose working in mainstream specialties.They emphasised, however, that theywould need to have a clinical genomicistin their multidisciplinary teams. Ideallythey would like us all to subspecialise,learning to “speak their language” andparticipate in their clinical networks. Thisis because they see us in an advisory rolefor more complex cases. They stressedthe need for us, working with scientists toprovide them with standardised laboratoryreports which convey a clear messageand are easy to interpret, stressingclinically actionable results. In essence,they see a role for us in clinicalinterpretation before reports are actuallysent out to them. They would also like thegenomic medicine service to be there topick up the pieces for more puzzling orcomplex cases or where results are moredifficult to explain (The term “rescuecounselling” came up more thanonce).They are confident that they cancounsel straightforward cases but feelthat they have limited abilities to docomplex counselling, investigate extendedfamilies and recognise dysmorphicfeatures. They are already well versed inclinical trials but can see an increasingrole for the genomicist in the clinic trialsteam.

Perhaps the most eye-openingpresentation for us was from JudeHayward, a GP with a special interest ingenetics from Yorkshire. She led usthrough a day in the life of an average GPand how applying genomic medicinewould fit into this. A GP works in timeslots of 10 minutes in a paperlessenvironment. Any model for delivery ofgenomic medicine in primary care has totake this into account but with theinnovative use of IT it is possible and GPsdo foresee that they will have a role. It

"as a specialty we need to leadchange in the genomics era"


way you want to. Even if you don’tcontinue to write programs yourself postyour PhD, these skills will stand you inexcellent stead when interacting withbioinformaticians and interpreting theresults from genomic testing in the future.

So how do you learn a computerprogramming language?

1. Do a course to learn the basics2. Have a mentor who can help you 3. Have a problem to solve4. Use online help sites5. Persevere

Develop your resilience: Research canbe tough, one of the most vital skills todevelop is resilience, work on this. Everylegendary scientist I have met or heardtalk has been through difficult times andthought about giving up, but somethingmade them keep going. Find yoursomething.

And finally, trying to advance knowledgeof humans (even just a little bit) andultimately help patients is an immenseprivilege, good luck. But remember, all ofthis is just my advice, and of course, youdon’t have to take it.

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members what it’s like to work with them,look at their track record of success:What journals do they publish in? Howmany of their PhD students completedtheir degrees? Are they accessible? Howdo they run their group meetings? Is thisa place where you can talk, think andgrow scientifically? Take your time tomake decisions about supervisors andprojects. Two or three years is a longtime.

Try it out: If time and funding permits, trya project out for a month or more to seewhether you like it and whether you aregood at it. Not everyone enjoys lab workor learning to program; the best way tofind out is to try it.

Know your strengths and yourweaknesses: Know yourself and play tothe things you excel at, and minimiseexposure to your weaker areas. Also tryto understand what the project entailsand how it will fit into your life. Someprojects, for example cell work, mightinvolve lab work at weekends. Could youcommit to this?

Bring clinical knowledge and skills: Asa clinician you are behind your scientificcolleagues in terms of exposure toscience. What you can bring to the arenathough is a wealth of clinical knowledge,skills and experience, and the value ofthis should not be underestimated.

Learn to program: In these days wheregenomic data are flooding in, learning acomputer programming language (suchas UNIX, Perl, Python or R) is an excellentskill for Clinical Geneticists to have. Iflearning to program makes sense withyour PhD project then do so! Being ableto write your own programs gives you thefreedom to interrogate data in exactly the

Have you ever thought about doing a PhDor MD or do you have a trainee who isthinking about it? Maybe it’s time to startexploring options and possibilities?

When embarking on a research projectyou can’t know exactly what you will find(if anything at all), or whether thecompetition will beat you to it, or all thechallenges you will face. What you can dothough, is to set yourself up with a goodsupervisor to cross unchartered scientificterritories with and a project that gets youexcited, and see where that takes you.But how do you even go about doingthat?

Explore: When I was searching for aPhD, many colleagues gave me extremelyhelpful advice. Speak to as many peopleas you can, in fact never stop speaking topeople about research, science is aboutsharing ideas and collaborating and this isjust the beginning of the journey.

What do you find interesting? Who workson this? Be creative, can you bring yourown previous work into a PhD? Don’tforget, you can apply for data from theDDD project, what questions could youask? Visit potential supervisors, or wisepeople you think might be able to helpyou. Don’t be discouraged if a meetingdoesn’t go the way you expected, this isall part of a longer journey and a learningexperience in itself. Enjoy this time; therewill be meetings that make you feelexcited. Thank people who have kindlygiven you their time to give you researchadvice, but remember you don’t alwayshave to take it. What you want from aresearch project is unique as you are.

Find a great person to work with: Findyourself someone who inspires you andsomeone you get on with. Ask their group

How to choose a PhD and reasons why Clinical Geneticistsshould learn to programWendy Jones, Clinical PhD student Wellcome Trust Sanger Institute

Apps for geneticsMary O’Driscoll, Birmingham


brain involvement in your favourite syndrome.The free version looks great or upgrade to apaid version available for those of us with acerebral obsession.

BIOGENE (free)A phone based search appfor gene information fromEntrez Gene at NCBIproviding referenced

information on gene function. Requireswifi/3G to access much of the information.

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where they link to management or diagnosticguidelines. Unfortunately this capacity islimited by access to internet and, for me,universal wifi coverage can’t come quicklyenough.

What else is out there? There are a few otherapps to tempt.

GROWTH CHARTS UK-WHO (free)Smart and simple phone appfrom the paediatriciansbehind the paediatrics.co.uk

website. Based on the up to date WHOgrowth chart data, input the date of birth,measurements, gender and gestation for aninstant centile calculation. Not so useful forthose whose growth falls outside the normalparameters however, so don’t get rid of yourpaper copies yet.

PROBAND (paid)Clear and intuitive pedigreedrawing software app foriPad with built-in HPO data,quick data input and free text

panel. The lack of individual identifiers (nameand date of birth) keeps it anonymous.Useful both in whipping up a quick and tidyfamily tree to annotate later or to add polishto a presentation.

ORPHANET (free)Who wouldn’t love theorphanet app? Available forphone and iPad it's useful onthe go and in clinic to look up

the occasional surprise in the patient's family.Some functions such as diagnostic testinformation require wifi/3G to access.

3D-BRAIN (free/paid)An interactive, annotated 3Dbrain image app. Considerthis if you ever have to explain

TGCAIt used to be that the mostinteresting thing in my clinickit, and only for smallchildren, was a retractable

measuring tape with ladybirds on. It seemsthat I may have found something that mightkeep the whole family involved. TGCA (TheGenetic Counselling App) is a tablet-basedvisual aid for genetic counselling in the clinicenvironment and a new alternative to theincreasingly battered folder of useful images Ihave carried to clinic for the last few years.Thanks to the technically talented folks at StGeorges, TGCA is a paid genetics app for ustechnically-challenged neophiles. Tablettechnology is ubiquitous. If you don’t haveone to hand ask your nearest medicalstudent and download the app for iPad.

What does it provide? Animations based onthree common areas covered in a geneticsconsultation; mendelian inheritance, commongenetic tests (including arrays) andchromosomes. Navigating the optionsavailable is straightforward with differentspeeds for the animations, a pause buttonand a choice of colours for the inheritedchromosome. I wasn’t immediately sure ofthe reason for the latter until, having decidedto try it out in clinic, I got one of my youngerpatients to join in and choose the variables.An immediate hit. It was popular withteenagers too and is certainly a suggestionfor those young people who are morereluctant to engage in conversation. Clearly,using an app cannot replace the face to faceaspect of an appointment, but like ourprinted copies acts as a useful adjunct. Usinganimations rather than static images certainlymade me re-adjust my usual clinic patter.

The app links directly to other resourcesincluding Unique and GeneReviews. This Ican envisage being useful for non-geneticsspecialists too in the management ofcommon genetic disorders, particularly

CGS News Editor


Derek LimConsultant Clinical Geneticist

West Midlands Regional Genetics ServiceNorton CourtBirmingham Women’s NHS Foundation TrustBirmingham B15 2TG

Tel: 0121-6272630Email: [email protected]: @UnknownVariant


FundingThe CGS has several bursaries availableto assist trainees in gaining furtherexperience. A complete list can be foundon the CGS website athttp://www.clingensoc.org/information-education/trainees/trainee-bursaries/ andare detailed below. These includebursaries for a great opportunity to visitanother centre either in the UK orinternationally as a short elective periodincluded in our training. Please contactthe CGS office via email [email protected] for more details onhow to apply.

1. Bursary to attend another centre (UK or abroad) £400 x 3

2. Bursary to attend BSGM conference x 2

3. Bursary for study leave – meeting or work £400 x 3

4. Robin Winter SpR Prize £200

Social mediaThere is now a CGS trainee facebookgroup athttps://www.facebook.com/groups/GeneticTraineeUK/ kindly set up by RhodaAkilapa (Sheffield). This is a closed groupso approval will be needed. In addition,the Yahoo Genetic SpR group continues,please contact me on the email addressbelow if you would like to join this group.The CGS twitter account @clingensoc isalso still going strong.

The future of Clinical GeneticsThank you to everyone who joined thediscussions on Facebook and the Yahoogroup about the future of clinicalgenetics. Thank you also to everyonewho completed our survey, kindly put

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TraineeColumnHannah Titheradge, Birmingham

CGS InternationalScholarshipDr Neerja Gupta (MD, DM Medical Genetics)Division of Genetics, Department of Pediatrics, AIIMS, New Delhi

• The important role played by geneticcounsellors was very much evident.Because of their counselling work, theburden on the clinicians is much lessand they can therefore focus moreinto basic and applied research.

• Diagnosis of most dysmorphicsyndromes is clinical backed up bythe availability of specific genetic teststhat further improves the clinicalacumen.

• Concept of transition clinics forvarious inherited metabolic disorderswas quite thoughtful and stresses theimportance of liaison betweenmetabolic specialists and adultphysicians after a particular age.

During the scholarship, I was given theopportunity to present interesting cases atthe dysmorphology meeting held inLondon on 13 March 2013. I alsoattended the CGS Spring meeting (14March 2013) in London. Both thesemeetings were a huge learningexperience. I presented my posterentitled The application of chromosomalmicroarrays in managing developmentaldelay in a major genetic centre in India.The presentation was well appreciated.

To conclude, this scholarship was a greatlearning experience. It gave me insightsfor improving the clinical genetics servicesat our centre in India. For this, I will bealways thankful to the CGS. Last but notleast it will be my future endeavor toestablish long lasting mutually beneficiallinks between the unit at Manchester andthe All India Institute of Medical Sciences,New Delhi, India.

I can still remember that late October2012 evening, when I received a letterfrom Dr Elisabeth Rosser, informing that Ihave been awarded the UK ClinicalGenetics Society (CGS) InternationalScholarship. I was delighted at thethought of being able to have a firsthandexperience of clinical genetics work in theUK. Dr Rob Elles was instrumental infinalising a schedule that would help memake the most out of my trip. I choseManchester as my visit centre since it wasthe place where exciting work was beingdone in the fields of dysmorphology andmetabolic disorders; my areas of interest.During my visit to St Mary’s hospital atManchester, I met several renowneddysmorphologists such as Dian Donnai,Jill Clayton-Smith, Brownyn Kerr andseveral others. I met the Willink metabolicteam notably Dr John Walter, Dr AndrewMorris, Dr Simon Jones and DrUmaramaswami. I was deeply touched bythe warmth and hospitality of the entireClinical Genetics Department of St Maryhospital. I attended their routineprescheduled meetings, their clinics andward rounds. As I had expected, both theinfrastructure and work culture in Clinicalgenetics at Manchester was amazing.

At Manchester, I noticed severaldifferences in work patterns, of which thenotable ones were-

• Apart from having big, spacious, wellequipped cytogenetics, molecular, andbiochemical genetics labs the majordifference that I noted was that eachclinical geneticist had identified anarea of sub-specialisation and all theirenergies were concentrated in thatparticular area.


On arriving in Birmingham, Louise wastedno time in reviewing the genetics servicefor paediatrics in the West Midlands andestablished regular general geneticsclinics and joint neurometabolic clinics atBirmingham Children’s Hospital. Louisealso contributed nationally todysmorphology, as a facilitator at theNational Dysmorphology meetings atGreat Ormond Street Hospital in Londonand founded the very successful MidlandsDysmorphology Group. Louise workedtirelessly to provide the very best servicepossible for patients and most recentlywas instrumental in providing the case forintroducing microarray analysis in toroutine service in Birmingham. She wasalso very active in research, alwaysstriving to improve knowledge for thegood of patients.

Sadly, Louise became ill in 2011 and hadto retire due to ill health in 2013. Shefought her illness with characteristiccourage and humour and continued to bea regular visitor to the department,contributing to clinical meetings andteaching of trainees for as long as shecould.

Louise was a dedicated and loyalcolleague who was passionate about herwork, patients and family. She had greatclinical acumen and was always willing tohelp and advise her colleagues andtrainees. She will be greatly missed by hercolleagues, patients, family and friends.She is survived by her husband Phil, andsons Greg and Matt.

Louise Anne Brueton: Consultant ClinicalGeneticist, Birmingham Women’s NHSFoundation Trust and Honorary SeniorLecturer, University of Birmingham. b. 1961 d. 23 September 2014

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Obituary – Dr Louise Anne Brueton 1961-2014Jenny Morton, Birmingham

Louise was born in Birmingham andattended medical school at the Royal FreeHospital, London. She graduated in 1984and continued her training in paediatricsat the Queen Elizabeth Hospital forChildren, Hackney and St Thomas’Hospital, London. She entered genetics in1987 with an MRC Fellowship under BobWilliamson at St Mary’s Hospital andRobin Winter at the Kennedy GaltonCentre and was then appointed as Seniorregistrar at the Kennedy Galton Centre in1989. She was awarded her MD thesisentitled Craniodigital syndromes andChromosome 7p in 1996 and was madea fellow of the Royal College of Physiciansin 1999. She was appointed as aconsultant Clinical Geneticist at theKennedy Galton Centre in 1993 and thenmoved to Birmingham, the city of herbirth, schooling and marriage, in 2000. Itis here that I had the privilege of workingwith her.

together by Anna Znaczko (Belfast). Itwas very interesting to hear everyone’sviews. It appears that many of us feel weneed additional training, particularly inbioinformatics, pharmacogenetics andstatistics, to better equip us for thisfuture. There are certainly plans in motionto try to help us bridge this gap and weawait further information on this.

Anna, Emily, Verity, Vicky and Irepresented the trainee views at therecent joint meeting between the CGScouncil and the Lead Clinicians. We willsend out further information about theconclusions of this meeting when thereport has been drafted.

CGS Council SpR representativesThere are currently two traineerepresentatives on the CGS council. I amdue to finish my stint on the council atthe end of this year, so please watch outfor elections at the beginning of 2015! Ihave been very grateful for theopportunity to sit on the councilrepresenting trainees nationally andwould strongly urge interested trainees toapply. There is also the possibility tobecome involved in sub-committees ofCGS, which I would also recommendwhere possible.

Views and IssuesIf you have any views that you would likediscussed nationally at the CGS councilmeetings, please contact myself([email protected]) or EmilyCraft ([email protected]). Trainingissues should be directed to the SACrepresentatives, Verity Hartill and VictoriaMcKay.


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Editorial

in the media. Later in the newsletter wehave a short piece from Anna Beach,genetic counsellor, on a patient supportday organised earlier this year for patientsand families with Lynch syndrome.

The Royal College of Pathologists havepresented best practice guidelines thatsuggest that all bowel cancers in patientsbelow the age of 50 years should betested for the presence of a mutation in amismatch repair gene. Such a change inpractice will undoubtedly have an impacton cancer genetics services all over thecountry. Whilst this would be a positivemove as more families with Lynchsyndrome would be identified, it isimportant that we are mindful of potentialconflicts which could arise from this. Howwill we ensure that patients are aware thatthey are undergoing a test that couldhave implications in terms of their ownfuture cancer risks, and which may alsohave implications for their relatives?

The question above is one that is oftenasked in relation to mainstreaming incancer genetics. Daniel Riddell andProfessor Nazneen Rahman haveprovided us with a useful Update on theMainstreaming Cancer Genetics (MCG)Programme that they are leading at theInstitute of Cancer Research, inpartnership with the Royal Marsdenhospital. Their MCG programme seems tohave successfully addressed thisquestion.

Those of you who were at the CGGWinter Meeting in December will haveheard Sam Smith from the WolfsonInstitute of Preventative Medicine give apresentation on the ENGAGE study. Thestudy aims to explore decision-making inbreast cancer chemoprevention. Thestudy also aims to investigate how NICE

guidelines on chemoprevention have beenimplemented across the country. This isan important new study that many of uscould contribute to. Please read Sam’sarticle to find out how you could getinvolved!

We also have a bit of an internationaltheme to our newsletter this time. Wehave a contribution from a TraineeGenetic counsellor from Jordan who iscurrently on a clinical attachment withJulian Adlard in Leeds, Sian Jenkins,trainee Genetic Counsellor reports fromthe ASHG conference in San Diego, andKelly Kohut reports on research findingsfrom North America presented byProfessor Steven Narod at BSGM inLiverpool in September 2014.

Lastly, Fiona Lalloo, chair of CGG gives usa summary of some of the great work thatthe CGG steering committee and otherswithin the group have undertaken over thepast year.

Munaza Ahmed, CGG News Editor

Welcome to the latest edition of the CGGnewsletter. Myself and Helen Hansonhave recently taken over as the editors ofthis section of the BSGM newsletter, wehope you’ll find our first edition aninteresting read. We’d like to thank EmmaWoodward and Andrew Cuthbert, ourpredecessors, for all their hard work indelivering previous editions.

The lead article is an interesting andthought-provoking piece by ProfessorAnneke Lucassen on the challenges ofconsent as we approach the era ofgenomic testing in a clinical setting.Anneke explores how differences in thelanguage surrounding consent can alterthe context in which that consent istaken. Anneke makes the important pointthat that just because a patient hasconsented to a test or procedure doesnot mean that they necessarily have theright to access to that test. Issues aroundconsent are relevant to our daily work andthis is a timely piece as the challenges oftaking meaningful consent are increasing,as the ways in which we are able to offergenetic testing become moresophisticated. Anneke has set-up and isthe chair of a BSGM sub-committee thatwill hopefully be able to provide ourcommunity with guidance in thischallenging arena.

The article by Ian Frayling on Systematictesting for Lynch syndrome in all patientsdiagnosed with bowel cancer below theage of 50 years, and potentially beyondthat age, is also timely as it comes sixmonths after the death of StephenSutton, an exceptional young mandiagnosed with bowel cancer at 15 yearsof age due to Lynch syndrome. Stephen’sexperience has not only led to a verysuccessful fundraising campaign but hasalso raised the profile of Lynch syndrome


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Consent and genetic testing: What is good enough for genomics?Anneke LucassenProfessor of Clinical GeneticsWessex Clinical Genetics Service and CELS unit (Clinical Ethics and Law, Southampton)

There are some clear legal landmarks in thisevolution: Thirty years ago, Sidaway case1

established that the information that shouldbe provided to a patient would bedetermined by the application of the ‘Bolam2

Test’; that is, what a reasonable body ofmedical opinion would agree would besufficient for patients to make an informeddecision. Aside from the obviouspaternalism inherent in this ruling, theproblems for such a test in a rapidlydeveloping clinical practice such asgenomics are obvious. The Bolitho3 casechallenged the principle of the Bolam testconsidering information to be adequate if itis what a reasonable patient might want toknow. Lord Woolfe, in Pearce v UnitedBristol Healthcare NHS Trust4 ruled that “thereasonable doctor must tell the patient whatthe reasonable patient would want to know”.So, what does the reasonable patient wantto know about genomics, and how can areasonable patient decide at the point oftesting what they would or would not wantto know? What is the reasonable healthprofessional able to tell a patient aboutgenomics, especially when most outputs arefar less deterministic than popular portrayalsmake them sound?

The other thing we need to remember isthat the consent process is not amechanism for enabling a patient to choosewhatever investigation they want. Whilstpatients can, and should be able to, refusemedical treatments they cannot havewhatever treatment or investigation theywant. Just because a patient wants to betested for breast cancer genes does notmean that respecting their right to self-determination means we are obliged toprovide them with that test. Wanting a testand consenting to it are not the same thing.Consent in this setting has to be more thansimple permission giving, particularlybecause we have evidence from established

predictive genetic testing programmes that aperson’s initial wishes are often different totheir considered decision. It also has to bemore than a signature on a form.Documentation of discussions in a patient’snotes may sometimes provide betterevidence of consent than a signature on aform. As Grubb5 also points out “valid legalconsent is given even where the patientdoes not demonstrate [her] agreementproviding that the state of mind was, in fact,that [s]he agreed. In other words, anunexpressed actual consent in law is a validconsent”

Our job as health professionals is to try andensure our patients’ choices are as informedas possible and this may mean highlightingsome difficult issues. This is particularly sofor the vexed topic of ‘incidental findings’ ingenomics. The reactions to the ACMGguidance earlier this year were veryfocussed on giving patients the right to say‘no‘ to certain findings, and less on whetherit is really possible to provide consent andrefusal to a range of possible unknownfindings. Patients should, of course, be ableto say ‘no’ to certain things, but this ‘no’should be an informed one and therefore theconsent process needs to be more than atick box exercise. This also means that if ahealth professional is not convinced therefusal was sufficiently informed, and harm ismore likely to be prevented by disclosure(through availability of surveillance or otherinterventions) then such refusal does nothave to be observed at all costs.

Confusion about what consent should looklike in medical practice more widely is in partreflected by the number of qualifiers oradjectives we place in front of the word:‘Informed consent’; ‘fully informed consent’,‘sufficient’ and ‘real’ are all to some extenttautologies since they are also part of thedefinition of consent itself: surely consent is

What does consent mean in the context ofgenome analysis? What are the importantelements of consent in the age of genepanels, whole exomes and genomes? Adiscussion about the potential risks andbenefits of analysing a particular part of thegenetic code (because of signs, symptomsor a particular family history of disease) willbe different to that about a whole genomeanalysis, where the range of possibleinferences that can be made, and thedegrees of certainty of many of them, aremuch greater. How can we possibly ensureconsent in these settings is ‘fully informed’,and, anyway, what does this mean? Thesequestions are important, and take on agreater significance as we move tomainstream genomics and as ourapproaches change from targeted to‘trawling’ analyses.

The Department of Health states “it is ageneral legal and ethical principle that validconsent must be obtained before startingtreatment or a physical investigation” andNHS choices tells us that “for consent to bevalid, it must be voluntary [not due topressure by staff, friends or family], informed,and the person consenting must have thecapacity to make the decision”. So ifconsent is only valid if the implications of [aninvestigation] are communicated andunderstood, can consent to genomic testingbe valid when the number of possibleoutcomes and inferences are much greaterthan can feasibly be discussed up front, letalone fully assimilated and their implicationsunderstood?

Providing consent to an investigation ortreatment is an important part of a person’sright to self-determination. A greater focuson consent over the last few decades alsoreflects changing attitudes about what isviewed as acceptable practice and a desireto move away from medical paternalism.


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Systematic testing forLynch syndrome Ian Frayling, Consultant Genetic Pathologist, All-Wales Medical Genetics Service

Earlier this summer “A systematic reviewand economic evaluation of diagnosticstrategies for Lynch syndrome” waspublished, shortly after a similar piece ofwork in The Netherlands.1,2 The NHShealth technology assessment, whichruns to 448 pages with the 16appendices, indicates that it would,according to the NICE reference case, becost-effective for the NHS to implementsystematic testing of colorectal cancersfor Lynch syndrome. In other words, thecost of finding new cases of Lynch wouldbe less than the maximum of £20,000 perQuality Adjusted Life Year (QALY) gained,the level at which new therapies andtechnologies are judged worthwhile toimplement (in The Netherlands their limitis €80,000 or ~£65,000).

The study looked at six different testingstrategies (combinations of MSI,immunohistochemistry and BRAF/MLH1methylation), compared with doingnothing. It also looked at simply testingincident cases of bowel cancer formutations in the four mismatch repairgenes (MSH2, MLH1, MSH6 and PMS2)– although doing this in reality would notbe the current way of doing things, wecould model this in silico to see how itcompares.

The results based on testing all cancersup to age 50 show that of all the tumourtesting-based strategies considered, MSI,followed by BRAF, and then referral toclinical genetics was the most cost-effective at £5,500 per QALY, whereassimply ‘sequencing’ everyone would cost£83,000/QALY. However, all strategiesbased on tumour testing came in wellbelow £10,000/QALY. Increasing the agecutoff to 60 years, would cost£7,700/QALY for MSI/BRAF, and even upto age 70 years it would still be only£10,800, well below the £20k threshold.

So, one way of looking at this is that if itwas a new cancer drug there would be anexcellent case for its introduction. TheNetherlands work shows similarly that itwould be cost-effective for them toincrease the age at which testing is doneto age 70, however, the yield of Lynchdrops off considerably over this age andfor a given amount of resources it wouldprobably be better to test incident casesof endometrial cancer, women who havehad both colorectal and endometrial atany age, and other rare Lynch-associatedtumours, such as small bowel andhepatobiliary cancers.

It was also determined that whilst thecost-effectiveness was improved byextending genetic testing to relatives, itwas actually cost-effective merely to findindex cases, because of the differenttreatment they would then receivereducing their risks of metachronouscancers.

In countries such as Denmark in whichthis is already being undertaken theresults are encouraging. There they donot have an upper age cutoff and recentdata presented at the 7th EuropeanMultidisciplinary Colorectal CancerConference shows ~3.2% of all colorectalcancers are due to Lynch, withapproximately equal numbers of casesattributable to each of the four genes,unlike the experience of genetics clinicswhere case referral is biased towardsearly onset and complete penetrance.

In July this year the Royal College ofPathologists Minimum Dataset forColorectal Cancer (aka best practiceguidelines) was updated, with the SAChaving sight of the NHS health economicanalysis, and now states that testing of allcolorectal cancers in the UK up to age 50for deficient mismatch repair must be

not really consent unless it is informed?Then, there are adjectives like specific,generic, open ended, broad, presumed orimplied which might be placed before theword consent in an attempt to nuance thenature of consent. If health professionals canbe well enough attuned and responsive todifferent situations and different levels ofunderstanding, then perhaps, likeWinnicott’s good enough parenting, weshould be striving for good enough consent.

References1. Sidaway v Board of Governors of the

Bethlem Royal Hospital (1984) QB 493,(1984) 1 All ER 1018, CA; affd (1985) AC871, (1985) 1 All ER 643, HL

2. Bolam v Friern Hospital ManagementCommittee (1957) 1 WLR 582 (QB)

3. Bolitho v Hackney Health Authority(1998) Ac 232, (1997) 4 All ER 771, HL,(1998) 39 BMLR 1

4. Pearce v United Bristol Healthcare NHSTrust (1999) PIQR 53; (1998) 48 BMLR118

5. A. Grubb, Consent to treatment, thecompetent patient. Principles of medicallaw, I Kennedy and A Grubb (eds) OUP(1998)


49CGG News

"according to NICE (it would) be cost-effective for the NHS to implementsystematic testing of colorectal cancers forLynch syndrome"

carried out.3 It acknowledges that thecase for testing all cases up to age 70 isestablished (in part also because of theprognostic and predictive value), but thatuntil funding is identified bycommissioners it cannot be demanded.

On the basis of this, and coinciding with itbeing six months since the death ofStephen Sutton at age 15 from bowelcancer due to Lynch syndrome, BowelCancer UK has launched a “Never tooyoung” campaign including systematictesting for Lynch, as a part of which manycolleagues have given their support in anopen letter to The Daily Telegraph. BowelCancer UK hope that all services will sooncomply with the RCPath minimum datasetand an age cutoff of 50 years, togetherwith sufficient provision of colonoscopicsurveillance, following which the agecutoff will rise to 70. However, for that tohappen it will ideally require a co-ordinated approach to implementationacross the four NHSs of the UK, andsome central funding to start it off,bearing in mind that the ultimate aim is toprevent as many expensive and life-shortening cancers as possible.

It has to be borne in mind however, thatwe were only able to consider the abilityof colonoscopy andhysterectomy/oophorectomy as life-savingprocedures, and also that the costs oftesting are constantly coming down. Alliedto this, aspirin prophylaxis promises toreduce mortality from all Lynch cancersand vaccines against MSI tumours maywell be on the way. So, the cost-effectiveness of finding cases of Lynchcan only increase.

References1. Snowsill, T, et al. A systematic review

and economic evaluation of diagnosticstrategies for Lynch syndrome. HealthTechnology Assessment 18.58 (2014):1-406.http://www.journalslibrary.nihr.ac.uk/hta/volume-18/issue-58

2. Sie, AS, et al. Fourfold increaseddetection of Lynch syndrome byraising age limit for tumour genetictesting from 50 to 70 years is cost-effective. Annals of Oncology 25.10(2014): 2001-2007.

3. http://www.rcpath.org/publications-media/publications/datasets/colorectal-cancer.htm

4. http://www.bowelcanceruk.org.uk/never-too-young/lynch-syndrome-testing-and-bowel-cancer/


50CGG News

cancer who received BRCA tests throughthis pathway showed that:

• 100% (77/77) were happy they hadthe test

• 99% (76/77) were happy to have thetest through oncology

Every woman with ovarian cancer offereda BRCA test chose to have testing. 17%of women with ovarian cancer testedwere found to have a BRCA mutation.The results of the pilot phase of thisimplementation are currently being writtenup for publication in early 2015.

The mainstream gene testing pathwayhas now been adopted as standardpractice by the breast and gynae units ofThe Royal Marsden; all women with non-mucinous ovarian cancer, and all womendiagnosed bilateral breast cancer <50yrs,Triple-negative breast cancer <50yrs orbreast and ovarian cancer at any age arenow routinely offered BRCA testing viaoncology as a standard part of their care.

We are now investigating how to furtherincrease access to gene testing for othergenes and other cancers. In particular weare planning to make the mainstreamBRCA testing criteria for breast cancer atThe Royal Marsden more permissive, sothat many more people can benefit.

The programme has made the fullmainstream pathway and trainingmaterials available through theprogramme website(www.mcgprogramme.com/brcatesting)so that other units can make use of them.

The work being carried out on theprogramme was highlighted by PaulBurstow, MP for Sutton & Cheam, during

a Westminster Hall Debate on 4November 2014. Mr Burstow told thedebate that the programme “shows thatproductivity is increased by doing thetesting as part of an oncologyappointment, rather than as somethingseparate. The trials are delivering that in away that is not costing the NHS more,and it is having huge benefits.”

The Mainstreaming Cancer Genetics(MCG) Programme is a cross-disciplinary,translational initiative to develop theassays, informatics, clinical infrastructure,education, ethics and evaluation that willallow implementation of (germline) cancergenetic testing into the routine clinicalcare of cancer patients and their relatives.The programme is led by The Institute ofCancer Research (ICR) in partnership withThe Royal Marsden and funded by theWellcome Trust. The programme will rununtil 2016.

A key aspiration of the programme is todevelop clinical pathways which allowmore people with cancer, and theirfamilies, to benefit from cancerpredisposition gene (CPG) testing.

Towards this objective, we havedeveloped a ‘mainstream’ gene testingpathway, which gives people with cancerthe option of having CPG testing throughtheir routine oncology appointments. Inthis model, CPG tests are carried out bymembers of the cancer team who havecompleted an online training coursedeveloped by the programme. Anyone inwhom the CPG test shows a pathogenicmutation automatically has anappointment with genetics, so that theimplications for themselves and theirfamilies can be discussed further. Thosewithout pathogenic mutations can alsohave appointments with genetics shouldthey wish to.

We have now fully implementedmainstream BRCA gene testing forwomen with breast and ovarian cancer atThe Royal Marsden.

Over 250 people have now receivedBRCA tests through the mainstreampathway. A survey of women with ovarian

Update on the MainstreamingCancer Genetics programmeDaniel Riddell, Programme Manager, Mainstreaming Cancer Genetics and Professor Nazneen Rahman, Head of Cancer Genetics, The Royal Marsden NHS Foundation Trust, Head of the Division of Genetics and Epidemiology, The Institute of Cancer Research


51CGG News

Following the publication of the NICEfamilial breast cancer guidelines in 2013, anew option for breast cancer risk reductionbecame available to women at elevatedrisk of the disease. This announcementcame after the publication of multiplerandomised controlled trials whichdemonstrated a reduction in breast cancerincidence among women taking SelectiveOestrogen Receptor Modulators (SERMs).The magnitude of the risk reduction fromSERMs was estimated to be 38% in asubsequent meta-analysis.1 The NICEguidance outlined that healthcareprofessionals within specialist geneticsclinics should offer one of two SERMs,Tamoxifen or Raloxifene, to women at highrisk of breast cancer, and considerationshould be given to making thesemedications available to women atmoderate risk.

Chemoprevention is undoubtedly a usefuladdition to the options available to womenat elevated risk of breast cancer. However,at a time when patients are alreadyengaging with unfamiliar information, thedecision to take chemoprevention may beburdensome. In addition to the standardcounselling available during consultations,patients will be asked to processinformation about the risks and benefits ofchemoprevention, and make a decisionthat fits with their personal preferences. Forthe majority of patients who are unfamiliarwith even basic health information, thedecision to take chemoprevention will be adifficult one. Furthermore, we all carry ourown preconceptions about health andillness, and our tolerance of risks andbenefit varies widely. To what extent willthese psychological factors contribute topatient’s thoughts about chemopreventionand its use?

Decision-making in breastcancer chemoprevention:The ENGAGE studyDr Sam Smith, Cancer Research UK Postdoctoral Fellow, Centre for Cancer Prevention,Queen Mary University of London, Wolfson Institute of Preventive Medicine

In an interdisciplinary collaboration fundedby Cancer Research UK, the ENGAGEstudy was formed to investigate questionssuch as these. Using a mixture of one-to-one interviews and surveys with patientsand clinicians, the ENGAGE study willinvestigate how breast cancerchemoprevention is being implementedacross the UK. Over the next six monthswe are recruiting clinicians to take part in abrief interview study investigating how theNICE guidelines have been interpreted inlocal settings. If you would like to help uswith this research, please email Dr SamSmith ([email protected]). We wouldalso like to hear from you if your clinic isinterested in assisting with recruitment for aplanned patient survey. Starting in May,2015 we are aiming to approachapproximately 3000 women who are atincreased risk of breast cancer to give ustheir perspective on chemoprevention.Baseline recruitment will be open for oneyear, with planned follow-ups at twomonths and one year. As a CancerResearch UK funded study, the ENGAGEstudy is eligible for National Institute forHealth Research (NIHR) portfolio funding tosupport centres that are able to help. Withyour help, we hope to gain an insight intohow chemoprevention can be integratedinto clinical care, and how women can bebest supported during the decision-makingprocess.

References1. Cuzick J, Sestak I, Bonanni B et al.,

(2013) Selective oestrogen receptormodulators in prevention of breastcancer: an updated meta-analysis ofindividual participant data. Lancet, 381:1827-34.


52CGG News

A Jordanian trainee's perspectiveon cancer genetics servicesLama Abujamous, Trainee Genetic Counsellor supervised by Julian Adlard, Consultant Clinical Geneticist, Leeds

other specialists. In the future, we will aimto provide genetic counselling support forthese services and enable access togenetic testing in line with internationalstandards.

In relation to the educational and trainingprogramme, I have begun a six monthclinical attachment in the YorkshireRegional Genetics Service based inLeeds, under the supervision of Dr JulianAdlard and his team. My background is inlaboratory science including a Master’sdegree in molecular biology and humangenetics. The aim of the attachment is toobtain experience of cancer geneticcounselling as practised in the UK. Thisincludes gaining understanding of riskassessment methods, availability ofgenetic testing, screening or preventiveoptions, and discussion with patients andtheir other responsible healthprofessionals. We should be aware ofpsychological and emotional issues, andpotential consequences of the testresults. Confidentiality of geneticinformation is very important.

I have gained experience in these aspectsthrough attending clinics and otheractivities with different members of theteam. I have also spent time in theRegional Genetics Laboratory observingthe available testing, including advancedtechniques such as Next GenerationSequencing and Capture Array cancerpanel testing, along with analysismethods and reporting.

KHCC has focussed on treatment ofpatients already affected with cancer,whereas I have learned that much more ofthe work in Cancer Genetics is directed atassessing risk in unaffected familymembers. This would lead to a change intypes of patient seen and we will consider

referral pathways for unaffected at-riskpatients to KHCC.

The future level of demand in Jordan isnot yet certain, but it is likely to increaseas more members of the public becomeaware. Also, medical staff at KHCCalready recognise hereditary issues andwish to refer patients for assessment andpossible genetic testing. There arechallenges to introducing wider germlinegenetic testing, but we will aim to developa Next Generation Service for genetictesting ‘in house’ in the near future. I amlooking forward to working withcolleagues to develop this further inJordan when I complete my attachment.

Five and a half billion of the world's 7.1billion population live in developingcountries. Most of these people do nothave access to services that couldprovide genetic counselling anddiagnostic tests for familial cancer risk. Itis expected that, over time, servicescurrently available in developed countrieswill become increasingly availableelsewhere.

King Hussein Cancer Center (KHCC) inJordan is one of the most specialisedcentres in the Middle East dedicated tothe treatment of paediatric and adultcancer patients. KHCC was established in1997, as a non-governmental, not-for-profit comprehensive cancer careorganisation. KHCC currently treats morethan 3500 new patients per year, and in2015 a new expansion is due to openwhich will increase the capacity to about9000 new cases per year. Limitedgermline cancer genetic testing iscurrently available from an externalprovider in specific circumstances.However, there is no comprehensivecancer genetics counselling or testingservice. We have a molecular diagnosticand immunogenetics laboratory. Thisprovides a range of testing, but notcurrently germline DNA analysis.

The KHCC vision and strategic planincludes improving access to education,training, and research in collaboration withinternational centres. We will aim to setup a cancer genetic counselling andtesting service. As breast cancer is themost common genetic cancer, we maystart with this type of cancer, and thenexpand to other cancers with a familialtendency and known predisposing genes.Within KHCC there are sub-specialisedservices for different sites of cancer,managed by oncologists, surgeons and


53CGG News

The ASHG meeting in SanDiego: A Trainee GeneticCounsellor ExperienceSian Jenkins, Trainee Genetic Counsellor, Wessex Clinical Genetics Service

One study from the University ofWashington, presented the benefits andchallenges of using multi-gene panels byreporting their study into two multi-genepanels, one containing 19 genes, the othercontaining 51 genes. Although the 51 genepanel identified actionable mutations in10% of patients who had already hadBRCA1 and BRCA2 testing and 13% ofpatients with pathogenic or likelypathogenic variants, it also identified 10%with variants of uncertain significance.Similar figures were also produced by the19 gene panel with 13% of patientscarrying variants of uncertain significance.The increasing frequency in which this typeof genetic testing is taking place in geneticshere in the UK is likely to continue providingus with some uncertain and trickyinformation to interpret on behalf of ourpatients.

I was also interested to hear thecomparison of genetic testing criteria in theUnited States to here in the UnitedKingdom. In particular, one speakerpresented their figures on the number offemales with triple negative breast cancerrelated to BRCA1 and BRCA2 genemutations. American guidelinesrecommend testing all individuals with triplenegative breast cancers under the age of60, an additional twenty years on the agecriteria provided by the NICE guidelines.The speaker explained that their studyfound that 24% of triple negative breastcancers over the age of 40, in the absenceof a family history, have a BRCA genemutation, suggesting the need for anincrease in the age threshold required forBRCA1/2 testing here in the UK.

The conference was a great experience asa trainee genetic counsellor and left mewith lots of food for thought as well as newfriends across the pond.

In October this year I attended the 64thAnnual American Society of HumanGenetics meeting in San Diego. Theconference held over 5 days was attendedby over 8000 delegates and was packedwith exhibitions, poster presentations,invited speakers and interactive activities.The conference was a great opportunity forme to learn about the excitingdevelopments currently being made in thefield of cancer genetics, and to networkwith our overseas colleagues.

The topics for concurrent speaker sessionswere vast and covered most aspects ofgenetics. From neuropsychiatric disordersto circadian disorders, the genetics ofobesity to reproductive genetics, it wasdifficult to make the most of the expertiseon offer and some careful timetabling wasneeded to make the most of theexperience.

A focus on cancer genetics was evident inthe programming, with a session based incancer genetics in almost all of the sevenconcurrent platform sessions. Thesesessions varied from a focus on genomicalterations of tumours to cancer typespecific topics such as hereditary breastand ovarian cancer. The conference alsohad almost 300 poster presentationsbased in the field of cancer genetics,making it one of the most representedfields within the conference.

A significant emphasis on the use of wholeexome or whole genome and its clinicalutility for our patients was evident in manyof these posters and sessions. With thedevelopment of multi-gene panels and itsincreasing use in clinical genetic testing Iwas interested to hear about theexperiences and challenges others havehad.


54CGG News

BSGM Annual Conference: Symposium by Dr Steven Narod on themanagement of hereditary breast cancer Kelly Kohut, Genetic Counsellor, Royal Marsden Hospital

While survival benefit for bilateralmastectomy has not been found in thegeneral population,2 the optimal treatmentfor BRCA carriers seems to be bilateralmastectomy at diagnosis, which preventslocal recurrence, contralateral breastcancer and improves survival. In womenwith stage 1-2 breast cancer and aBRCA1/BRCA2 mutation, most fatalcancers between years 15 to 20 of follow-up were from contralateral breast cancer.3

In the UK, we counsel carriers about theoption of bilateral mastectomy but thedecision is ultimately patient choice. Moreinformation about survival benefit mayinfluence decision-making about risk-reducing surgery in future.

Impact of BSO on mortalityIn addition to preventing ovarian cancer,BSO reduces the risk of all cause mortality,which included a benefit from reducingbreast cancer recurrence, death andsecond primary breast cancer.4 BSOseems to be particularly effective inreducing death in BRCA1 mutation carrierswith oestrogen receptor negative breastcancers (up to 70%), but this requiresfurther study. Dr Narod’s group looked atwomen who chose not to have BSObecause they wanted to have a child afterbreast cancer treatment. Pregnancy did notimpact survival, but BSO significantlyincreased survival.5

A 4% risk of ovarian cancer was reported ifBRCA1 mutation carriers waited until age40 to have BSO, while the risk before age35 was only 1%.4 This supported therecommendation in North America toconsider BSO by age 35, which differsfrom The Royal Marsden recommendationto consider from age 40. In our patientpopulation, many women have not hadchildren yet and therefore desire forchildren needs to be balanced with the low

risk of ovarian cancer below 40 years. In2013, over half (51%) of all UK live birthswere to mothers aged 30 and over and theaverage age of all mothers increased to30.0 years (www.ons.gov.uk). Therefore it isimportant to take into consideration bothside effects of an early menopause andreproductive decisions and provide patientswith appropriate information.

Should all BRCA1 mutation carriersreceive chemotherapy?The survival of 455 BRCA1 mutationcarriers with node negative, 0-2cm grade 1breast cancer was much poorer thanexpected.6 The survival in those who hadchemotherapy was 90% compared to 75%in those who did not have chemotherapy.The addition of chemotherapy increasedthe survival rates compared to non-carrierswith similar grade 1 cancer. Dr Narodconcluded that all BRCA1 mutation carrierswith breast cancer (even those with a goodprognosis cancer) should havechemotherapy, and we need moreinformation on platinum-basedchemotherapy.

In a trial in Poland of BRCA1-associatedstage 1-3 breast cancer treated with neo-adjuvant cisplatin, 61% had completepathologic response.7 This compared to amuch lower rate of 20% or less in womentreated with standard regimes. It is thoughtthat there may be a similar effect in triplenegative or basal type breast cancer. DrNarod’s group are planning further study inMexico where the mutation frequency ishigh.8

In the UK, it is not yet standard practice togive cisplatin with small, node negativebreast cancer, although this approach isstarting to be used at some centres, mainlyin the context of clinical trials. More data isawaited from the San Antonio Breast

Dr Steven Narod is Director of the FamilialBreast Cancer Research Unit at Women'sCollege Research Institute in Toronto. Hepresented at the BSGM conference inLiverpool in September 2014 on hisresearch involving women with hereditarybreast cancer. We attended his talk withinterest as many of his findings haveimpact for clinical practice and we wereinterested to see how practice varies inCanada compared to the UK. The maintopics he discussed are outlined below.

Predictors of contralateral breast cancer riskDr Narod commented that in Canada 24%of women with breast cancer (regardless ofgenetic status) are choosing to havebilateral mastectomy, and this was due topatient choice rather than surgicalrecommendation. In the UK, NICErecommend that rapid genetic testing atdiagnosis should only be performed as partof a research study, but breast teams areincreasingly requesting testing to aidmanagement decisions.

In a study of 810 women with stage 1-2breast cancer and a BRCA1 or BRCA2mutation, the risk of contralateral breastcancer was 42% for women under age40.1 Younger age at onset and familyhistory of breast cancer increased the riskof contralateral cancer, and tamoxifen orbilateral salpingo-oophorectomy (BSO)decreased the risk. In 20 years of follow-up, 60% had a new event (recurrence ornew primary in the ipsilateral orcontralateral breast) while 40% of womenwho chose ipsilateral mastectomy still hada new event. Dr Narod concluded therewas not a strong rationale for choosingipsilateral mastectomy at time of diagnosisbecause the main benefit came frompreventing contralateral breast cancer.


55CGG News

LynchsyndromesupportmorningAnna Beach, Genetic Counsellor, WessexClinical Genetics Service

3. Metcalfe K, Gershman S, Ghadirian P,Lynch HT, Snyder C, Tung N et al.(2014) Contralateral mastectomy andsurvival after breast cancer in carriers ofBRCA1 and BRCA2 mutations:retrospective analysis. BMJ11;348:g226. doi: 10.1136/bmj.g226.

4. Finch AP, Lubinski J, Moller P, SingerCF, Karlan B, Senter L et al. (2014)Impact of oophorectomy on cancerincidence and mortality in women witha BRCA1 or BRCA2 mutation. J ClinOncol 20;32(15):1547-53.

5. Valentini A, Lubinski J, Byrski T,Ghadirian P, Moller P, Lynch HT et al.(2013) The impact of pregnancy onbreast cancer survival in women whocarry a BRCA1 or BRCA2 mutation.Breast Cancer Res Treat 142(1):177-85.

6. Huzarski T, Byrski T, Gronwald J, GórskiB, Domagala P, Cybulski C et al. (2013)Ten-year survival in patients withBRCA1-negative and BRCA1-positivebreast cancer. J Clin Oncol10;31(26):3191-6.

7. Byrski T, Huzarski T, Dent R, MarczykE, Jasiowka M, Gronwald J et al. (2014)Pathologic complete response toneoadjuvant cisplatin in BRCA1-positivebreast cancer patients. Breast CancerRes Treat 147(2):401-5.

8. Torres-Mejia G, Royer R, LlacuachaquiM, Akbari MR, Giuliano AR, Martinez-Matsushita L et al. (2014). RecurrentBRCA1 and BRCA2 mutations inMexican women with breast cancer.Cancer Epidemiol Biomarkers Prev. Nov4. pii: cebp.0980.2013. [Epub ahead ofprint]

For six years the Wessex Clinical GeneticsService has held an annual supportmorning for BRCA mutation carriers. Theaim is to provide patients with theopportunity to meet one another andshare their experiences. Such days alsoallow us as a department to make contactwith mutation carriers annually to provideupdated relevant information. Feedbackfrom these days has always been verypositive. We therefore decided to providethe same opportunity for carriers ofmutations in mismatch repair genes.

The first, and unexpected challenge,came in naming the morning; ‘Lynch orHNPCC’? ‘carrier’? We decided on thetitle of ‘the Wessex Hereditary ColonCancer Information and SupportMorning’.

In total 60 people came. Some of theattendees hadn’t been seen in a geneticsclinic for a long time so it seemedimportant to re-cap the basics and givean overview of the condition andscreening recommendations. This provedessential as during Dr Ahmed’s talk therewas a great deal of interaction andquestions, all very encouraging for thesmall group discussions planned for later.We also invited, Sir John Burn to comeand talk about CAPP3. Again, thisprompted lots of discussion within thegroup.

We had sorted attendees into groupsprior to the day. Each group had amember of the clinical team there tofacilitate and answer questions. A mid-morning coffee break provided furtheropportunity for patients to talk to eachother in a less formal setting.

This patient support morning was reallyinteresting and provided a really valuable

Cancer Symposium. These potentialtreatment planning implications make itmore important to identify BRCA carriersearly on in breast cancer management.

Other genesDr Narod plans to create a new study ofPALB2 mutation carriers with breast cancerto examine survival, risk of contralateralbreast cancer and whether there is anindication for risk-reducing BSO.

ConclusionThis symposium provided usefulconsiderations for clinical practice. Betterdata on survival benefit may influencecounselling about risk-reducingmastectomy in future. BSO could beconsidered at age 35, depending on thepriorities of the individual. Cisplatinchemotherapy may become treatment ofchoice in BRCA1 carriers with breastcancer, even those with small nodenegative disease. Although we have knownabout the BRCA1 and BRCA2 genes for 20years, there is still much more to learn.Further research will help to guidemanagement recommendations in the UK.

References1. Metcalfe K, Gershman S, Lynch HT,

Ghadirian P, Tung N, Kim-Sing C et al.(2011). Predictors of contralateralbreast cancer in BRCA1 and BRCA2mutation carriers. Br J Cancer26;104(9):1384-92.

2. Kurian AW, Lichtensztajn DY, KeeganTH, Nelson DO, Clarke CA, Gomez SL.(2014) Use of and mortality afterbilateral mastectomy compared withother surgical treatments for breastcancer in California, 1998-2011. JAMA3;312(9):902-14.


56CGG News

CGG Chair’s Report Fiona Lalloo, CGG Chair and Consultant Cancer Geneticist, Department of GeneticMedicine, Manchester

2014 has been a busy year for all of us –the year started with the excellent meetingin Leiden for which we thank our hosts. Itwas a great opportunity to meet up withour Dutch colleagues, hear some fantastictalks and see a little of a beautiful city.

Jointly with CGS we undertook a survey ofthe clinical genetics trainees this year, totry to establish what the long-termaspirations of those currently training ingenetics are. We had a good responserate of 83% with 58 respondents.Disappointingly, only 12% of respondentswere members of CGG, as opposed to78% being members of CGS. Given thatabout 50% of the workload of a regionalgenetics service is cancer genetics, wewere surprised by this. About half thetrainees had a background in adultmedicine and half in paediatrics, withabout 30% of those in training alreadyhaving a higher degree and 50% or theremaining cohort hoping to gain oneduring their training. Whilst the majority oftrainees had training in specificsubspecialties led by a consultant with aspecific interest in that subspecialty, 50%of them want a general adult/paediatriccase mix as a consultant with a further20% wanting a mixed adult-only caseload. This may be related to the lack of adesire to move: the vast majority oftrainees wish for a consultant post eitherin the centre in which they are training, orin the same geographical region. Thisstrikes me as a little unrealistic and makesme wonder whether, as a profession, weare discussing long-term prospectsappropriately at entry into the trainingschemes. There was only one trainee whowished to subspecialise in cancer geneticsand it is therefore important that we inCGG consider how to encourage moretrainees into this branch of clinicalgenetics.

Nationally, there is a huge amount ofchange on the horizon with the tendersfor 100,000 genome project just in andthe NHS laboratory re-designationlooming. At the same time, we arecontinuing to run services whilst ensuringcost efficiencies – no mean task. TheNICE guidelines on familial breast cancerthat were published in June 2013 haveresulted in discrepancies around accessto genetic testing for BRCA1/2 across thecountry, with some centres being in aposition to implement testing at the 10%level, and others lacking capacity orfunding. NICE guidelines are just that –guidelines with no associated requirementfor funding. Members of CGG wereinvolved in a UKGTN workshop toestablish testing criteria, which alsoclearly discusses the need for testingindividuals with ovarian cancer. As amember of the medical genetics CRG, Ihave had input into an NHS policydocument putting forward the case forfunding testing at the 10% threshold. Theprocess around funding in the NHS hasproved to be enlightening, but has alsoemphasised the current economicdifficulties facing the NHS as a whole. Weawait the decision of the commissioners.

Other members of CGG have been busy:there has been a response to asomewhat misleading advert by Myriadgenetics in the BMJ; support for the HTAreport on widespread testing of colorectalcancers by IHC for MMR proteins andmembership of working parties fornational guidelines for childhoodendocrine tumours. We are also leadingthe national audit on management ofLynch syndrome.

So, 2014 has been a busy one! 2015looks the same, although the nationallandscape this time next year should be

insight into the challenges faced by thisgroup of patients. It gave attendees thechance to discuss with each other whatand how they told their children about thecondition, to what extent Lynch syndromeaffects their lives and their family stories.It was a privilege to be part of and hearthe discussions. Whilst the subject matterwas serious and often sad, theatmosphere of the day was generallyupbeat and supportive. Feedback fromthe attendees was constructive andpositive. Many wanted copies of theslides from the talks.

Due to the success of the morning weplan to hold another event next year. Iwould be very interested to hear aboutsimilar events that other GeneticsServices provide. We found the day arewarding experience which seems tohave met a need from our patients whichcannot be offered in a hospital clinicsetting.


57CGG News

clearer. CGG will continue to be involvedin national policies as well as continuingwith the remit of research. The springmeeting will be in Manchester and will bea joint meeting with the 14th IMPACH(International Meeting on the PsychosocialAspects of Hereditary Cancer). We hopeto see you there.

CGG News Editor


Munaza AhmedWessex Clinical Genetics ServicePrincess Anne HospitalUniversity Hospitals Southampton NHSFoundation TrustCoxford RoadSouthampton, SO16 5YA

Tel: 02381 206170Email: [email protected]


58BSHG News

Notes


59BSGM News

British Society for Genetic Medicine ChairmanMrs Angela [email protected] 0151 702 4294

Chair ElectProf Bill [email protected] 0161 276 4150

General SecretaryDr Adam [email protected] 020 7188 1394

TreasurerProf Peter [email protected]

Press Officer Ms Sarah [email protected] 020 7278 7870

Executive OfficerMrs Dina [email protected] 627 2634

Association for Clinical GeneticScienceChairDr Ann [email protected] 271 7004

Chair Elect

General SecretaryMr Simon [email protected] 329241

TreasurerDr David [email protected] 206 4642

Association of Genetic Nurses andCounsellorsChairDr Laura [email protected] 0121 627 2630

Vice ChairMs Anita [email protected] 01702 435555

SecretaryMr Peter [email protected] 0121 627 2630

TreasurerMiss Liwsi Kim [email protected] 01792 285972

Cancer Genetics GroupChairDr Fiona [email protected] 276 6322

SecretaryDr Lucy [email protected] 020 7762 6831

TreasurerDr Julian [email protected] 392 4452

Clinical Genetics SocietyPresidentProf Jill [email protected] 276 4150

Vice President Professor Ruth [email protected] 01173425107

General SecretaryDr Lynn [email protected] 708 9988

TreasurerDr Diana [email protected] 206162

Officers of the BSGM andconstituent societies

Human Skin Epidermoid Carcinoma Epithelial Cells (A-431) © Michael W Davidson, National High Magnetic Field Laboratory, Florida State University (http://micro.magnet.fsu.edu/primer/techniques/fluorescence/gallery/cells/a431/a431cellslarge.html)

The British Society for Genetic Medicine

Registered Charity Number 1058821

Administrative OfficeClinical Genetics Unit, Birmingham Women’s Hospital, Edgbaston, Birmingham B15 2TG

Tel 0121 627 2634Fax 0121 623 6971Email [email protected] www.bshg.org.uk

new the newsletter of issue 52 february 2015 bsgm news · 2015. 3. 3. · the newsletter of the...

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