title: Phenotypic variability in Friedreich ataxia: role of the associated GAA triplet repeat expansion.
abstract: We studied genotype-phenotype correlations in a group of 100 patients with typical Friedreich ataxia (FRDA), and in three groups of patients with atypical clinical presentations, including 44 Acadian FRDA, 8 late-onset FRDA (LOFA), and 6 FRDA with retained reflexes (FARR). All patients, except 3 with typical FRDA, carried two copies of the FRDA-associated GAA triplet repeat expansion. Overall, the phenotypic spectrum of FRDA appeared to be wider than defined by the currently used diagnostic criteria. Our study indicated the existence of several sources of variability in FRDA. Patients with larger GAA expansions tended to have earlier onset and were more likely to show additional manifestations of the disease. Mitotic instability of the expanded GAA repeats may partially account for the limited degree of correlation between expansion sizes as determined in lymphocytes and clinical parameters. Some clinical variants associated with specific FRDA haplotypes, such as Acadian FRDA and FARR, turned out to be unrelated to expansion sizes. No polymorphism in the frataxin coding sequence could be associated with these clinical variants.
authors.affiliation: Centre de Recherche Louis-Charles Simard, Montreal, Quebec, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Montermini
authors.forename: A
authors.initials: A
authors.lastname: Richter
authors.forename: K
authors.initials: K
authors.lastname: Morgan
authors.forename: C M
authors.initials: CM
authors.lastname: Justice
authors.forename: D
authors.initials: D
authors.lastname: Julien
authors.forename: B
authors.initials: B
authors.lastname: Castellotti
authors.forename: J
authors.initials: J
authors.lastname: Mercier
authors.forename: J
authors.initials: J
authors.lastname: Poirier
authors.forename: F
authors.initials: F
authors.lastname: Capozzoli
authors.forename: J P
authors.initials: JP
authors.lastname: Bouchard
authors.forename: B
authors.initials: B
authors.lastname: Lemieux
authors.forename: J
authors.initials: J
authors.lastname: Mathieu
authors.forename: M
authors.initials: M
authors.lastname: Vanasse
authors.forename: M H
authors.initials: MH
authors.lastname: Seni
authors.forename: G
authors.initials: G
authors.lastname: Graham
authors.forename: F
authors.initials: F
authors.lastname: Andermann
authors.forename: E
authors.initials: E
authors.lastname: Andermann
authors.forename: S B
authors.initials: SB
authors.lastname: Melançon
authors.forename: B J
authors.initials: BJ
authors.lastname: Keats
authors.forename: S
authors.initials: S
authors.lastname: Di Donato
authors.forename: M
authors.initials: M
authors.lastname: Pandolfo
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D004247:DNA / Q000032:analysis; D018450:Disease Progression; D005621:Friedreich Ataxia / Q000145:classification* / Q000453:epidemiology / Q000235:genetics*; D005838:Genotype; D006801:Humans; D010641:Phenotype; D018911:Trinucleotide Repeats
chemical_list: D004247:DNA