Molecular analysis of new mutations for Huntington's disease: Intermediate alleles and sex of origin effects

Y. P. Goldberg, B. Kremer, S. E. Andrew, J. Theilmann, R. K. Graham, F. Squitieri, H. Telenius, S. Adam, A. Sajoo, E. Starr, A. Heiberg, G. Wolff, M. R. Hayden

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)174-179
Number of pages6
JournalNature Genetics
Volume5
Issue number2
DOIs
Publication statusPublished - 1993

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint

Dive into the research topics of 'Molecular analysis of new mutations for Huntington's disease: Intermediate alleles and sex of origin effects'. Together they form a unique fingerprint.

Cite this