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

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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. Ann Neurol 2004;56:898–901
Funding Information
  • NIH (National Institute of Neurological Disorders and Stroke) (NS047596)
  • American Diabetes Association
  • Oklahoma Center for the Advancement of Science and Technology