Repeat instability in the 27-39 CAG range of the HD gene in the Venezuelan kindreds: Counseling implications
| Autor: | David E. Housman, Nancy S. Wexler, S.R. Snodgrass, Steven M. Hersch, H. D. Rosas, D Brocklebank, Stacey S. Cherny, Lon R. Cardon, J. B. Penney, Maria A. Ramos-Arroyo, S A Roberts, Jang-Ho J. Cha, J M Andresen, Javier Gayán, Andrew Feigin, Anne B. Young |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male congenital hereditary and neonatal diseases and abnormalities Adolescent Genetic counseling Genetic Counseling Nerve Tissue Proteins Penetrance Biology Article Young Adult Cellular and Molecular Neuroscience chemistry.chemical_compound Huntington's disease medicine Huntingtin Protein Humans Family Age of Onset Allele Child Alleles Genetics (clinical) Aged Aged 80 and over Genetics Nuclear Proteins Middle Aged Venezuela medicine.disease Psychiatry and Mental health Huntington Disease chemistry Female Age of onset Trinucleotide Repeat Expansion Penetrant (biochemical) Trinucleotide repeat expansion |
| Zdroj: | American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. :425-429 |
| ISSN: | 1552-485X 1552-4841 |
| Popis: | The instability of the CAG repeat size of the HD gene when transmitted intergenerationally has critical implications for genetic counseling practices. In particular, CAG repeats between 27 and 35 have been the subject of debate based on small samples. To address this issue, we analyzed allelic instability in the Venezuelan HD kindreds, the largest and most informative families ascertained for HD. We identified 647 transmissions. Our results indicate that repeats in the 27-35 CAG range are highly stable. Out of 69 transmitted alleles in this range, none expand into any penetrant ranges. Contrastingly, 14% of alleles transmitted from the incompletely penetrant range (36-39 CAGs) expand into the completely penetrant range, characterized by alleles with 40 or more CAG repeats. At least 12 of the 534 transmissions from the completely penetrant range contract into the incompletely penetrant range of 36-39 CAG repeats. In these kindreds, none of the individuals with 27-39 CAGs were symptomatic, even though they ranged in age from 11 to 82 years. We expect these findings to be helpful in updating genetic counseling practices. |
| Databáze: | OpenAIRE |
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