Friedreich's ataxia is an autosomal recessive disorder characterized by
spinocerebellar degeneration. It is caused by an unstable GAA trinucleotide repeat expansion (>120 repeats) in the first intron of the
frataxin gene on chromosome 9 (9q13) in both alleles. Concentric
left ventricular hypertrophy has been recognized as the major cardiac manifestation of
Friedreich's ataxia. Our aim was to investigate the influence of the
frataxin repeat length on
cardiac hypertrophy in patients with
Friedreich's ataxia and in patients with hypertrophic and
dilated cardiomyopathy. Thirty-one patients with
Friedreich's ataxia, 86 patients with
hypertrophic cardiomyopathy, 134 patients with
dilated cardiomyopathy, and 32 healthy individuals without
cardiac disease were analysed by electrocardiography and 2D-M-mode echocardiography. Then, the size of the
frataxin repeat was determined by polymerase chain reaction (PCR) and
agarose gel electrophoresis. The number of GAA repeats in patients with hypertrophic and
dilated cardiomyopathy was not different from the length in patients without
cardiac disease (
hypertrophic cardiomyopathy, 8+/-2 repeats on GAA 1 allele and 11+/-5 repeats on GAA 2 allele;
dilated cardiomyopathy, 7+/-2 repeats on GAA 1 allele and 11+/-5 repeats on GAA 2 allele; Control, 9+/-1 repeats on GAA 1 allele and 12+/-6 repeats on GAA 2 allele). The septal and posterior wall thickness of these patients was not related to the GAA repeat length. All patients with
Friedreich's ataxia had two enlarged alleles with a mean GAA repeat length of 757+/-316 and 1012+/-231, respectively. The lengths of both alleles were significantly greater than the lengths in the controls (P<0.0001), patients with
hypertrophic cardiomyopathy (P<0.0001) and
dilated cardiomyopathy (P<0.0001). A significant correlation was revealed between interventricular septal
hypertrophy and
frataxin repeat length in the smaller allele. Furthermore, the ratio of septal to posterior wall thickness was significantly correlated to GAA repeat size on the smaller allele. In conclusion, the size of the GAA repeat on the smaller allele in the
frataxin gene is associated with the degree of
left ventricular hypertrophy in patients with
Friedreich's ataxia but is not related to the severity of
hypertrophic cardiomyopathy.