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.

SUBMITTER: Laccone F 

PROVIDER: S-EPMC1288149 | biostudies-literature | 2000 Mar

REPOSITORIES: biostudies-literature