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Friedreich ataxia in carriers of unstable borderline GAA triplet‐repeat alleles
Author(s) -
Sharma Rajesh,
De Biase Irene,
Gómez Mariluz,
Delatycki Martin B.,
Ashizawa Tetsuo,
Bidichandani Sanjay I.
Publication year - 2004
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20333
Subject(s) - allele , ataxia , genetics , trinucleotide repeat expansion , phenotype , biology , mutation , gene , neuroscience
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