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(Circulation. 1997;95:2247-2249.)
© 1997 American Heart Association, Inc.

Articles

Correlation Between Left Ventricular Hypertrophy and GAA Trinucleotide Repeat Length in Friedreich's Ataxia

Richard Isnard, MD; Hanna Kalotka, MD; Alexandra Dürr, MD; Mireille Cossée, MD; Michèle Schmitt, PhD; Françoise Pousset, MD; Daniel Thomas, MD; Alexis Brice, MD, PhD; Michel Koenig, MD, PhD; Michel Komajda, MD

Service de Cardiologie, Association Claude Bernard (R.I., H.K., F.P., D.T., M. Komajda), Fédération de Neurologie, INSERM 289 (A.D., A.B.), Hôpital Pitié-Salpétrière, Paris; Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France (M.C., M. Koenig); and Laboratoire de Génétique Moléculaire des Eucaryotes, Strasbourg, France (M.S.).

Correspondence to Pr Komajda, Service de Cardiologie, Hôpital Pitié-Salpétrière, 47 Blvd de l'Hôpital, 75651 Paris Cedex 13, France.

Background Friedreich's ataxia (FA), the most common inherited ataxia, is associated frequently with cardiac hypertrophy, and death is often cardiac related. Recently, the disease has been associated with a mutation that consists of an unstable expansion of GAA repeats in the first intron of the gene encoding frataxin on chromosome 9.

Methods and Results We studied 44 consecutive patients with FA, determined the size of GAA expansions in the frataxin gene, and examined the relation between the genotype and cardiac phenotype assessed by M-mode and two-dimensional echocardiography. All the patients were homozygous for the mutation. The size of the GAA expansion on the smaller allele varied from 270 to 1200. We found a correlation between the size of GAA expansion and the left ventricular wall thickness (r=.51, P<.001) and the left ventricular mass index (r=.45, P=.002). Left ventricular hypertrophy was observed in 81% of patients with a number of GAA repeats above the median value of 770 compared with only 14% in the other group (P=.002).

Conclusions These data demonstrate that in FA, the severity of left ventricular hypertrophy is related to the number of GAA repeats. These results suggest that abnormalities of the gene encoding frataxin, a protein of unknown function highly expressed in the normal heart, may play an important role in the modulation of cardiac hypertrophy.

Key Words: genetics • hypertrophy • cardiomyopathy • echocardiography

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