Wednesday, April 4, 2007

New Mutations For Huntington's Disease From Advanced Paternal Age

: Nat Genet. 1993 Oct;5(2):174-9. Links
Comment in:
Nat Genet. 1993 Nov;5(3):215.
Molecular analysis of new mutations for Huntington's
disease: intermediate alleles and sex of origin effects.Goldberg YP, Kremer B, Andrew SE, Theilmann J, Graham RK, Squitieri F, Telenius H, Adam S, Sajoo A, Starr E, et al.
Department of Medical Genetics, University of British Columbia, Vancouver, Canada.

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.

PMID: 8252043 [PubMed - indexed for MEDLINE]


Nature Genetics 5, 174 - 179 (1993)
Molecular analysis of new mutations for Huntington's disease: intermediate alleles and sex of origin effects
Y. Paul Goldberg1, Berry Kremer1, Susan E. Andrew1, Jane Theilmann1, Rona K. Graham1, Ferdinando Squitieri1, Håkan Telenius1, Shelin Adam1, Anaar Sajoo1, Elizabeth Starr1, Arvid Heiberg2, Gerhard Wolff3 & Michael R. Hayden1
1Department of Medical Genetics, University of British Columbia, 416−2125 East Mall Vancouver, British Columbia V6T 2C1, Canada

2Frambu Helsesenter, 1404 Siggerud, Norway

3Institut für Humangenetik und Anthropologie, Universität Freiburg, Breisacherstrasse 33, D-7800 Freiburg, Germany

Correspondence should be addressed to M.R.H.

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