what is in your genes? anna frangulov, b.s. research coordinator children’s hospital boston
TRANSCRIPT
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 [email protected]@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 [email protected] or [email protected]