title: A recurrent expansion of a maternal allele with 36 CAG repeats causes Huntington disease in two sisters.
abstract: Large intergenerational repeat expansions of the CAG trinucleotide repeat in the HD gene have been well documented for the male germline. We describe a recurrent large expansion of a maternal allele with 36 CAG repeats (to 66 and 57 repeats, respectively, in two daughters) associated with onset of Huntington disease (HD) in the second and third decade in a family without history of HD. Our findings give evidence of a gonadal mosaicism in the unaffected mother. We hypothesize that large expansions also occur in the female germline and that a negative selection of oocytes with long repeats might explain the different instability behavior of the male and the female germlines.
authors.affiliation: Institute of Human Genetics, 37073 Göttingen, Germany. flaccon@gwdg. de
authors.forename: F
authors.initials: F
authors.lastname: Laccone
authors.forename: W
authors.initials: W
authors.lastname: Christian
mesh_terms: D000328:Adult; D017668:Age of Onset; D000483:Alleles; D005260:Female; D005838:Genotype; D006801:Humans; D006816:Huntington Disease / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009030:Mosaicism / Q000235:genetics; D009035:Mothers; D010063:Ovum / Q000378:metabolism; D010375:Pedigree; D012727:Sex Characteristics; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*