title: Friedreich ataxia in carriers of unstable borderline GAA triplet-repeat alleles.
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.
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Sharma
authors.forename: Irene
authors.initials: I
authors.lastname: De Biase
authors.forename: Mariluz
authors.initials: M
authors.lastname: Gómez
authors.forename: Martin B
authors.initials: MB
authors.lastname: Delatycki
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ashizawa
authors.forename: Sanjay I
authors.initials: SI
authors.lastname: Bidichandani
mesh_terms: D000483:Alleles; D005260:Female; D005621:Friedreich Ataxia / Q000235:genetics*; D006580:Genetic Carrier Screening; D006801:Humans; D008297:Male; D008875:Middle Aged; D018911:Trinucleotide Repeats / Q000235:genetics*