Friedreich ataxia in carriers of unstable borderline GAA triplet-repeat alleles

Ann Neurol. 2004 Dec;56(6):898-901. doi: 10.1002/ana.20333.

Abstract

Friedreich ataxia patients are homozygous for expanded GAA triplet-repeats containing 66 to 1,700 triplets. We report two patients with delayed-onset, hyperreflexia and gradually progressive disease. Both were heterozygous for large expansions and also carried alleles with 44 and 66 triplet-repeats, respectively. Due to somatic instability, 15% (GAA-44) and 75% (GAA-66) of cells contained alleles with >/=66 triplet-repeats, constituting a plausible mechanism for their mild phenotype. A sibling with a stable GAA-37 allele and a large expansion was clinically normal. Instability of borderline alleles confers a risk for Friedreich ataxia, and the range of pathogenic alleles is broader than previously recognized.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles*
  • Female
  • Friedreich Ataxia / genetics*
  • Genetic Carrier Screening*
  • Humans
  • Male
  • Middle Aged
  • Trinucleotide Repeats / genetics*