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

Rajesh Sharma; Irene De Biase; Mariluz Gómez; Martin B. Delatycki; Tetsuo Ashizawa; Sanjay I. Bidichandani

doi:10.1002/ana.20333

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

Rajesh Sharma, Irene De Biase, Mariluz Gómez, Martin B. Delatycki, Tetsuo Ashizawa, Sanjay I. Bidichandani

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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.

Original language	English (US)
Pages (from-to)	898-901
Number of pages	4
Journal	Annals of Neurology
Volume	56
Issue number	6
DOIs	https://doi.org/10.1002/ana.20333
State	Published - Dec 2004

ASJC Scopus subject areas

Neurology
Clinical Neurology

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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.",

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AU - Sharma, Rajesh

AU - De Biase, Irene

AU - Gómez, Mariluz

AU - Delatycki, Martin B.

AU - Ashizawa, Tetsuo

AU - Bidichandani, Sanjay I.

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

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