title: Molecular analysis of new mutations for Huntington's disease: intermediate alleles and sex of origin effects.
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.
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
authors.forename: Y P
authors.initials: YP
authors.lastname: Goldberg
authors.forename: B
authors.initials: B
authors.lastname: Kremer
authors.forename: S E
authors.initials: SE
authors.lastname: Andrew
authors.forename: J
authors.initials: J
authors.lastname: Theilmann
authors.forename: R K
authors.initials: RK
authors.lastname: Graham
authors.forename: F
authors.initials: F
authors.lastname: Squitieri
authors.forename: H
authors.initials: H
authors.lastname: Telenius
authors.forename: S
authors.initials: S
authors.lastname: Adam
authors.forename: A
authors.initials: A
authors.lastname: Sajoo
authors.forename: E
authors.initials: E
authors.lastname: Starr
mesh_terms: D000328:Adult; D017668:Age of Onset; D000483:Alleles; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D005600:Fragile X Syndrome / Q000235:genetics; D006801:Humans; D006816:Huntington Disease / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009223:Myotonic Dystrophy / Q000235:genetics; D010375:Pedigree; D012091:Repetitive Sequences, Nucleic Acid; D012727:Sex Characteristics
chemical_list: D017931:DNA Primers