Background Friedreich's ataxia, the most common inherited ataxia,is associated with a mutation that consists of an unstable expansionof GAA repeats in the first intron of the frataxin gene on chromosome9, which encodes a protein of unknown function.
Methods We studied 187 patients with autosomal recessive ataxia,determined the size of the GAA expansions, and analyzed theclinical manifestations in relation to the number of GAA repeatsand the duration of disease.
Results One hundred forty of the 187 patients, with ages atonset ranging from 2 to 51 years, were homozygous for a GAAexpansion that had 120 to 1700 repeats of the trinucleotides.About one quarter of the patients, despite being homozygous,had atypical Friedreich's ataxia; they were older at presentationand had intact tendon reflexes. Larger GAA expansions correlatedwith earlier age at onset and shorter times to loss of ambulation.The size of the GAA expansions (and particularly that of thesmaller of each pair) was associated with the frequency of cardiomyopathyand loss of reflexes in the upper limbs. The GAA repeats wereunstable during transmission.
Conclusions The clinical spectrum of Friedreich's ataxia isbroader than previously recognized, and the direct moleculartest for the GAA expansion on chromosome 9 is useful for diagnosis,determination of prognosis, and genetic counseling.
Source Information
From the Fédération de Neurologie and INSERM Unité 289, Hôpital de la Salpêtrière, Paris (A.D., Y.A., C.P., A.B.); the Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg (M.C., V.C., J.-L.M., M.K.); and the Centre Hospitalier Général de Saint-Pierre, Ile de La Réunion (C.M.) — all in France.
Address reprint requests to Dr. Brice at INSERM Unité 289, Hôpital de la Salpêtrière, 47 Blvd. de l'Hôpital, 75651 Paris CEDEX 13, France.
Genetic Abnormalities in Friedreich's Ataxia
Dutka D. P., Nunez D. J.R., Filla A., De Michele G., Cocozza S., Madhani H. D., Dürr A., Brice A., Koenig M., Rosenberg R. N.
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N Engl J Med 1997;
336:1021-1023, Apr 3, 1997.
Correspondence
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