1 / 18

Genetic aspects of stuttering

Genetic aspects of stuttering. Dr Bert Bast ( ex-University Hospital Utrecht Nl), with Dr Dennis Drayna (NIH, Bethesda Md) and Dr Simon Fisher (Max Planck Inst ., Nijmegen Nl) . Own experience. PWS, persistent but can manage Pharmacist → Immunology → Genetics

ketan
Download Presentation

Genetic aspects of stuttering

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Geneticaspects of stuttering Dr Bert Bast (ex-UniversityHospital Utrecht Nl), withDr Dennis Drayna (NIH, Bethesda Md) and Dr Simon Fisher (Max PlanckInst., Nijmegen Nl)

  2. Ownexperience • PWS, persistent butcan manage • Pharmacist → Immunology → Genetics • Head of LaboratoryUniversityHospital Utrecht Nl • Science • Health care • Quality system • Teaching • Organisation • Local, national, international

  3. FIRSTCONTRIBUTORS GENETICSEnvironment Speech Language Planning Production LATER CONTRIBUTORS Experience EXACERBATION Emotional Reactivity & Regulation OVERT BEHAVIOR Conture et al 2006 Instances of Stuttering

  4. Genes in Stuttering? • Known: it runs in families • Taken in the past as due to environment & education • Studies on mono/dizygotictwins and adoption: 45-84% inherited • How to find relevant genes? • Basicinformationexplained

  5. How to find relevant genes? • Genetictrait • Studies in families • Linkagechromosomal marker • Western families toosmall • Western society too diverse • Special families? • Consanguinous (inbred) forages in e.g. secludedvalleys

  6. Pakistani stuttering family PKST72 • ○: f; □: m; ∕: †; •▪: st • ==: consanguinous • Chromosomal markers ̴ stuttering • Cloningfragments • Sequencinggenes:

  7. Cells, chromosomes & genes • Body consists of cells • Eachcellcontains a nucleus • 46 chromosomes (human) • 2 m DNA in 10 μm nucleus (~ 20 km in tennis ball) • DNA: Nucleotides • Stretch N’s maybe a gene • 22.000 genes (human) • Duplicatedduringcelldivision • Sometimeserrors: mutation

  8. Severity of mutation • Most are repaired • Ifnot, lethal forcellitself • Or lethal beforebirth (abortus) • Or ̴ lethal duringchildhood • Orgivedisease in adults • Dependingonaffectedamino acid & mono vsdizygosity • Orpositive: evolution

  9. Mutatedgenes • Genesencode (via RNA) proteins (aminoacids) • Mutated gene maygiveaberrantprotein • Sometimesadvantage • In PKST72 mutations in gene calledGNPTAB • & otherenzymes (proteins) in lysosomalpathway • Cellclearance

  10. These mutations and stuttering • Action=reaction ̴ Newton? • Genesdon’tworkthatway • In PKST71 exeptions ↔ • Studies in USA & GB: • p=0.0004 significant not100%

  11. Significant, buthow? • FromPathology: in severemutationsenzymes ‘absent’: • Rare fatalchildhood disorder • Heremildmutations present • In laboratory studies mutant enzymes made & expressed: • Activitydecreased ̴ 50%

  12. Furthersignificance?? • These are commonenzymes • Howthenspecific effect? • More expressedlocally in brain • Little more known at present • Examplefuture studies • Martin Sommer & Gerry Maguire

  13. Where are we now? • HeredityStuttbeingfilled in • Known to existforyears • First geneselucidated • Found in different populationsworldwide • Statistically significant • Function ̴ stuttering studied • Accounts for ̴ 10% PWS • Othergenes?

  14. Stuttering loci and genes

  15. Somanygenesonedisease? • My own research in myeloma ( ̴ leukemia): • 7 firstlyimplicatedgenes; A 50 secondarygenes • Basedonthat: Diagnosis & therapy >>>> • E.g. in deafness 150 genes

  16. Working hypothesis • Specificbrainnervecells are unique to speech and uniquely sensitive to this mild metabolic deficit • Identify these cells, discover whatthey do, theirconnections and howthisinherited deficit affectsthem • It is not a black vs white pattern: learn to understand and utilize the plasticity of the (young) brain

  17. Implications • Society: stuttering is a medical issue, likemany • Parents: don’tfeelguilty, itisn’tyourfault • PWS: genes do notgive a doom, keep working • Scientists: diagnostic/prognosticsignificance? • SLP’s: therapeuticalsignificance? • Reinforce the medicalposition ̴physicaltherapist • Utilizeplasticity: earlyintervention (M-C Franken) • Understanding of pathophysiologywill help to improve diagnosis and treatment

  18. Acknowledgements • Dr Dennis Drayna NIH • Dr Simon Fisher MPI • 100’s of scientists • 1000’s of PWS • Millions of bucks • Insight and hope

More Related