what is in your genes? anna frangulov, b.s. research coordinator children’s hospital boston

What Is In Your Genes?What Is In Your Genes?

Anna Frangulov, B.S. Research CoordinatorAnna Frangulov, B.S. Research Coordinator

Children’s Hospital BostonChildren’s Hospital Boston

Why Hearing Loss is Why Hearing Loss is So Common?So Common?

Structure of the EarStructure of the Ear

Sound wave

Hair Cell the Cochlea “snail”

Extensions

Hair Cell

Structure of the EarStructure of the Ear

Conductive HL Sensorineural HL

Genetic

• Infections

• Drug-Related

• Structural

What Causes Hearing Loss?

• Unknown

• Traumas/ Exposures

Non-Genetic

How Genetic HL occurs?How Genetic HL occurs?

Chromosomes in NucleusChromosomes in Nucleus

23 Pairs of Chromosomes

MOM DAD

One Chromosome PairOne Chromosome Pair

Genes“instruction manual”

Genes

Chromosome PairChromosome Pair

Genes

Mutation“error”

How Is Mutation Passed On How Is Mutation Passed On (Inherited)?(Inherited)?

Recessive Recessive ~80%~80% Dominant Dominant ~15%~15% X-Linked X-Linked ~2%~2% Mitochondrial Mitochondrial >2%>2%

Dominant Inheritance Dominant Inheritance

Mutation“error"

Hearing Hearing Loss

Hearing Loss Hearing Loss Hearing Hearing

Point #1Point #1

The risk rate is for The risk rate is for everyevery childchild

CarrierCarrier

Mutation“error"

Hearing

How a Recessive Mutation is How a Recessive Mutation is Passed?Passed?

Carrier –No Hearing Loss Carrier –No Hearing Loss

Affected Child—Hearing Loss

Recessive Inheritance Recessive Inheritance

Hearing Loss Hearing

Hearing Hearing

Hearing Hearing

Point #2Point #2

MostMost children with genetic cause of hearing loss children with genetic cause of hearing loss

are born to parents with normal hearingare born to parents with normal hearing

Sex ChromosomesSex Chromosomes

HearingHearing Loss

X-Linked Inheritance X-Linked Inheritance

HL

Mitochondrial Inheritance Mitochondrial Inheritance

Hearing Loss Hearing LossHearing Loss Hearing Loss

Hearing Loss

Every child has 50% Every child has 25%

Dominant InheritanceDominant Inheritance Recessive InheritanceRecessive Inheritance

Hearing Loss Hearing “Carrier”Hearing “Carrier”

X-LinkedX-Linked MitochondrialMitochondrial

Mutation is on X chromosome

All males have 50%

All children w/HL

Mother

HOW? WHO? WHY?HOW? WHO? WHY?

HOWHOW

Do We Know if HL is Genetic? Do We Know if HL is Genetic?

WHOWHO Should Have a Genetic Test?Should Have a Genetic Test?

Case A: SyphilisCase A: Syphilis

Case B: CMVCase B: CMV

Case C: PrematurityCase C: Prematurity

Case D: High bilirubin level Case D: High bilirubin level

Everybody with Sensorineural HLEverybody with Sensorineural HL

Also 2 Mutations in Cx26!!Also 2 Mutations in Cx26!!

Point #3Point #3

Even if you know your cause for hearing loss, you Even if you know your cause for hearing loss, you may also have an underlying genetic causemay also have an underlying genetic cause

WHYWHY

Should We Have a Genetic Test??Should We Have a Genetic Test??

BenefitsBenefits

a definite causea definite cause family members realize that they are family members realize that they are

carriers & determine risk factors for future carriers & determine risk factors for future childrenchildren

helps to find appropriate treatment/ helps to find appropriate treatment/ managementmanagement

does not necessarily find the answer does not necessarily find the answer severity of HL may not be predicted severity of HL may not be predicted a person may have mutations, but not have HLa person may have mutations, but not have HL

LimitationsLimitations

Things to ConsiderThings to Consider

Primary Care/ Pediatrician

ENT

Audiologist

Clinical GeneticistClinical Geneticist

Genetic CounselorGenetic Counselor

Clinical Molecular GeneticistClinical Molecular Geneticist

1.Talk to knowledgeable 1.Talk to knowledgeable professionalprofessional

Things to ConsiderThings to Consider

3. Cost3. Cost

2. What tests are done?2. What tests are done?Cx26Cx26Cx30Cx30Mitochondrial TestsMitochondrial TestsPendredPendred

UNDERSTANDING UNDERSTANDING TEST RESULTSTEST RESULTS

(example Cx26)(example Cx26)

What Does the Result Mean?What Does the Result Mean?

Two Mutations are FoundTwo Mutations are Found No Mutations are FoundNo Mutations are Found

Mutations w/Unknown Mutations w/Unknown Significance Significance

One Mutation is FoundOne Mutation is Found

??~10%

~70%~18%

~1%

One Mutation FoundOne Mutation Found

Mutation unrelated to deafnessMutation unrelated to deafness Test did not find 2Test did not find 2ndnd mutation mutation Dominant mutationDominant mutation There may be a mutation in another geneThere may be a mutation in another gene

Future in Genetics and HLFuture in Genetics and HL

More Genetic Tests More Genetic Tests

GeneChip TechnologyGeneChip Technology

Deafness GeneChip (Rehm Study): MYO7A, OTOF, MYO6, USH1C, PRES, TMPRSS3, TMIE, GJB2

Deafness GeneChip (Greinwald Study): MYO7A, OTOF, CHDH23, KCNE1, KCNQ1,PDS, GJB6, GJB2

Two GeneChips are available right now:

Things to RememberThings to Remember

Most children with HL are born to Most children with HL are born to parents with normal hearing parents with normal hearing

The risks rates is for The risks rates is for everyevery child child If you have other cause for hearing If you have other cause for hearing

loss you may also have an loss you may also have an underlying genetic causeunderlying genetic cause

A negative genetic test result = A negative genetic test result = inconclusiveinconclusive

Questions?Questions?

Research StudiesResearch Studies

Connexin 26 Study-Connexin 26 Study- individuals with Cx26 mutations individuals with Cx26 mutations

Genetic Testing and Counseling StudyGenetic Testing and Counseling Study - - If you or your If you or your child has had genetic testing for hearing loss and you child has had genetic testing for hearing loss and you are willing to fill out a questionnaireare willing to fill out a questionnaire

GeneChip Study - GeneChip Study - individuals with hearing loss who and individuals with hearing loss who and parents with normal hearing parents with normal hearing

Novel Gene Discovery StudyNovel Gene Discovery Study - - five or more family five or more family members with hearing lossmembers with hearing loss

Also in Spanish!

Educational Materials

http://hearing.harvard.edu

Helpful InformationHelpful Information

Genetic Counselor -Genetic Counselor - Rebecca Madore call 617-355-4534 to set an Rebecca Madore call 617-355-4534 to set an appointment or email appointment or email rmadore@partners.orgrmadore@partners.org

Department of Clinical GeneticsDepartment of Clinical Genetics – To make appointment with Clinical – To make appointment with Clinical Geneticist call 617-355-6394.Geneticist call 617-355-6394.

National Society of Genetic Counselors (NSGC)National Society of Genetic Counselors (NSGC) www.nsgc.orgwww.nsgc.org

Help us evaluate educational materialHelp us evaluate educational material

Research Study Participation & Booklets Orders: Research Study Participation & Booklets Orders: Anna Frangulov Anna Frangulov

617-515-2962 or anna.frangulov@childrens.harvard.edu617-515-2962 or anna.frangulov@childrens.harvard.edu