TY - JOUR
T1 - Friedreich ataxia in carriers of unstable borderline GAA triplet-repeat alleles
AU - Sharma, Rajesh
AU - De Biase, Irene
AU - Gómez, Mariluz
AU - Delatycki, Martin B.
AU - Ashizawa, Tetsuo
AU - Bidichandani, Sanjay I.
PY - 2004/12
Y1 - 2004/12
N2 - 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.
AB - 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.
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U2 - 10.1002/ana.20333
DO - 10.1002/ana.20333
M3 - Article
C2 - 15562408
AN - SCOPUS:9644303359
VL - 56
SP - 898
EP - 901
JO - Annals of Neurology
JF - Annals of Neurology
SN - 0364-5134
IS - 6
ER -