MOLECULAR ANALYSIS OF NEW MUTATIONS FOR HUNTINGTONS-DISEASE - INTERMEDIATE ALLELES AND SEX OF ORIGIN EFFECTS

Citation
Yp. Goldberg et al., MOLECULAR ANALYSIS OF NEW MUTATIONS FOR HUNTINGTONS-DISEASE - INTERMEDIATE ALLELES AND SEX OF ORIGIN EFFECTS, Nature genetics, 5(2), 1993, pp. 174-179
Citations number
25
Categorie Soggetti
Genetics & Heredity
Journal title
ISSN journal
10614036
Volume
5
Issue
2
Year of publication
1993
Pages
174 - 179
Database
ISI
SICI code
1061-4036(1993)5:2<174:MAONMF>2.0.ZU;2-T
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 investig ate sequential events underlying HD. We show the existence of an inter mediate 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 u nstable and in the sporadic cases, expand to the full mutation associa ted with the phenotype of HD. This expansion has been shown to occur o nly during transmission through the male germline and is associated wi th advanced paternal age. These findings suggest that new mutations fo r 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.