TY - JOUR
T1 - The GAA repeat expansion in intron 1 of the frataxin gene is related to the severity of cardiac manifestation in patients with Friedreich's ataxia
AU - Bit-Avragim, Nana
AU - Perrot, Andreas
AU - Schöls, Ludger
AU - Hardt, Cornelia
AU - Kreuz, Friedmar R.
AU - Zühlke, Christine
AU - Bubel, Stefanie
AU - Laccone, Franco
AU - Vogel, Hans Peter
AU - Dietz, Rainer
AU - Osterziel, Karl Josef
N1 - Funding Information:
Acknowledgements The authors are grateful all patients and their relatives for their excellent co-operation and willingness to participate in this study. We thank the German Heredo-Ataxie Society for their collaboration and support. N.B. was supported by the Deutscher Akademischer Austauschdienst (DAAD) grant, Freunde der Charité grant and Max-Delbrück-Center Fellowship. We thank to Dr. Annette E. Ellmer, Dr. Simone Cordini, Dr. Imke Poepping and Dr. Bojara for the help in examining patients with Friedreich’s ataxia.
PY - 2001/1
Y1 - 2001/1
N2 - 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 GAA1 allele and 11±5 repeats on GAA 2 allele; dilated cardiomyopathy, 7±2 repeats on GAA1 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.
AB - 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 GAA1 allele and 11±5 repeats on GAA 2 allele; dilated cardiomyopathy, 7±2 repeats on GAA1 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.
UR - http://www.scopus.com/inward/record.url?scp=17744391751&partnerID=8YFLogxK
U2 - 10.1007/s001090000162
DO - 10.1007/s001090000162
M3 - Journal articles
C2 - 11269509
AN - SCOPUS:17744391751
SN - 0946-2716
VL - 78
SP - 626
EP - 632
JO - Journal of Molecular Medicine
JF - Journal of Molecular Medicine
IS - 11
ER -