Molecular analysis of new mutations for Huntington's disease: intermediate alleles and sex of origin effects
- 1 October 1993
- journal article
- Published by Springer Nature in Nature Genetics
- Vol. 5 (2) , 174-179
- https://doi.org/10.1038/ng1093-174
Abstract
Huntington's disease (HD) is associated with expansion of a CAG repeat in a novel gene. We have assessed 21 sporadic cases of HD to investigate sequential events underlying HD. We show the existence of an intermediate allele (IA) in parental alleles of 30-38 CAG repeats in the HD gene which is greater than usually seen in the general population but below the range seen in patients with HD. These IAs are meiotically unstable and in the sporadic cases, expand to the full mutation associated with the phenotype of HD. This expansion has been shown to occur only during transmission through the male germline and is associated with advanced paternal age. These findings suggest that new mutations for HD are more frequent than prior estimates and indicate a previously unrecognized risk of inheriting HD to siblings of sporadic cases of HD and their children.Keywords
This publication has 22 references indexed in Scilit:
- DNA analysis of distinct populations suggests multiple origins for the mutation causing Huntington diseaseClinical Genetics, 2008
- A PCR method for accurate assessment of trinucleotide repeat expansion in Huntington diseaseHuman Molecular Genetics, 1993
- Retreat of the triplet repeat?Nature Genetics, 1993
- A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomesCell, 1993
- Variation of the CGG repeat at the fragile X site results in genetic instability: Resolution of the Sherman paradoxCell, 1991
- New mutation to Huntington's disease.Journal of Medical Genetics, 1989
- Huntington's chorea arising as a fresh mutation.Journal of Medical Genetics, 1983
- A probable case of mutation in Huntington's disease.Journal of Medical Genetics, 1976
- Parental age effects on the occurrence of new mutations for the Marfan syndromeAnnals of Human Genetics, 1972
- Mutation in Huntington's chorea.Journal of Neurology, Neurosurgery & Psychiatry, 1969