부산대학교 도서관

Byline: Andreas Perrot (1), Hajo Schmidt-Traub (2), Bernard Hoffmann (2), Matthias Prager (2), Nana Bit-Avragim (1), Raisa I. Rudenko (3), Dinara A. Usupbaeva (3), Zhyldyz Kabaeva (1), Bakytbek Imanov (3), Mirsaid M. Mirrakhimov (3), Rainer Dietz (1), Anna Wycisk (4), Michal Tendera (4), Reinhard Gessner (2), Karl Josef Osterziel (1) Keywords: Hypertrophic cardiomyopathy; Beta-myosin heavy chain gene; Genotype--phenotype correlations Abstract: Hypertrophic cardiomyopathy (HCM) is a frequent, autosomal-dominant cardiac disease and manifests predominantly as left ventricular hypertrophy. Mutations in the cardiac beta-myosin heavy chain gene (MYH7) are responsible for the disease in about 30% of cases where mutations were identified. We clinically evaluated a large group of 147 consecutive HCM patients from three cardiology centers in Germany, Poland, and Kyrgyzstan according to the same protocol. The DNA of the patients was systematically analyzed in the whole coding region of the MYH7 gene using PCR, single-strand conformation polymorphism analysis, and automated sequencing. Eleven different missense mutations (including seven novel ones) in 11 unrelated patients were identified, showing a mutation frequency of 7.5% in the study population. We further examined the families of five patients (three of German, one of Polish, and one of Kyrgyz origin) with 32 individuals in total. We observed a clear, age-dependent penetrance with onset of disease symptoms in the fourth decade of life. Genotype--phenotype correlations were different for each mutation, whereas the majority was associated with an intermediate/malign phenotype. In conclusion, we report a systematic molecular screening of the complete MYH7 gene in a large group of consecutive HCM patients, leading to a genetic diagnosis in 38 individuals. Information about the genotype in an individual from one family could be very useful for the clinician, especially when dealing with healthy relatives in doubt of their risk about developing HCM. The increasing application of genetic screening and the increasing knowledge about genotype--phenotype correlations will hopefully lead to an improved clinical management of HCM patients. Author Affiliation: (1) Kardiologie am Campus Buch und Virchow-Klinikum, Charite-Universitatsmedizin Berlin und Max-Delbruck-Centrum fur Molekulare Medizin, Wiltbergstrasse 50, 13125, Berlin, Germany (2) Institut fur Laboratoriumsmedizin und Pathobiochemie am Campus Virchow-Klinikum, Charite-Universitatsmedizin, Berlin, Germany (3) National Center for Cardiology and Internal Medicine, Bishkek, Kyrgyzstan (4) Third Department of Cardiology, Silesian School of Medicine, Katowice, Poland Article History: Registration Date: 19/01/2005 Received Date: 18/06/2004 Accepted Date: 09/12/2004 Online Date: 22/04/2005 Article note: An erratum to this article can be found at http://dx.doi.org/10.1007/s00109-005-0722-9 Andreas Perrot and Hajo Schmidt-Traub contributed equally to this work