TY - JOUR
T1 - Phenotypic variability in friedreich ataxia
T2 - Role of the associated GAA triplet repeat expansion
AU - Montermini, Laura
AU - Richter, Andrea
AU - Morgan, Kenneth
AU - Justice, Cristina M.
AU - Julien, Dominique
AU - Castellotti, Barbara
AU - Mercier, Jocelyne
AU - Poirier, Josée
AU - Capozzoli, Fiorentino
AU - Bouchard, Jean Pierre
AU - Lemieux, Bernard
AU - Mathieu, Jean
AU - Vanasse, Michel
AU - Seni, Marie Hélene
AU - Graham, Gail
AU - Andermann, Frederick
AU - Andermann, Eva
AU - Melançon, Serge B.
AU - Keats, Bronya J B
AU - Di Donato, Stefano
AU - Pandolfo, Massimo
PY - 1997/5
Y1 - 1997/5
N2 - 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.
AB - 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.
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U2 - 10.1002/ana.410410518
DO - 10.1002/ana.410410518
M3 - Article
C2 - 9153531
AN - SCOPUS:17144467700
VL - 41
SP - 675
EP - 682
JO - Annals of Neurology
JF - Annals of Neurology
SN - 0364-5134
IS - 5
ER -