Prevalence of cardiac beta-myosin heavy chain gene mutations in patients with hypertrophic cardiomyopathy
| Autor: | Rainer Dietz, Bakytbek Imanov, Mirsaid M. Mirrakhimov, Karl Josef Osterziel, Nana Bit-Avragim, Bernard Hoffmann, Reinhard Geßner, Dinara A. Usupbaeva, Raisa I. Rudenko, Andreas Perrot, Zhyldyz Kabaeva, Hajo Schmidt-Traub, Michal Tendera, Matthias Prager, Anna Wycisk, Heiko Witt |
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| Rok vydání: | 2005 |
| Předmět: |
Adult
Male medicine.medical_specialty Pathology Adolescent Genotype DNA Mutational Analysis Molecular Sequence Data Mutation Missense Biology medicine.disease_cause Left ventricular hypertrophy Risk Factors Germany Internal medicine Drug Discovery Prevalence medicine Humans Missense mutation Amino Acid Sequence Prospective Studies Child Kyrgyzstan Genetics (clinical) Aged Mutation Myosin Heavy Chains Hypertrophic cardiomyopathy Cardiomyopathy Hypertrophic Middle Aged medicine.disease Penetrance Pedigree Molecular Medicine Population study Female MYH7 Poland Cardiac Myosins Sequence Alignment |
| Zdroj: | Journal of Molecular Medicine. 83:468-477 |
| ISSN: | 1432-1440 0946-2716 |
| DOI: | 10.1007/s00109-005-0635-7 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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