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Cardiomyopathies (CMP) clinically and genetically belong to the heterogeneous group of myocardial diseases. Among them, three major clinical forms (hypertrophic, dilated, and restricted) are distinguished. Genetic factors play a substantial role in the etiology of dilated and hypertrophic CMP; family cases constitute more than 20% of these forms. Most familial cases of CMP are inherited as an autosomal dominant character. Autosomal recessive and X-linked forms are rare. Genetic basis for rare familial forms of restricted CMP is unclear. There are forms with strict maternal inheritance, which suggests the involvement of the mitochondrial genome. The nature of several CMP forms was determined and a number of genetic loci for this disease was revealed by modern methods of genetic mapping. In familial hypertrophic cardiomyopathy (FHC), four genes have been identified (those of beta-myosin heavy chain, alpha-tropomyosin, cardiac troponin T, and myosin-binding protein C), all of which encode sarcomeric proteins. Maternally inherited forms of FHC are associated with mutations in the mitochondrial tRNA genes. Linkage analysis in familial dilated CMP revealed at least five genetic loci on chromosomes 1, 3, 9, and X. X-linked forms of dilated CMP are caused by mutations in dystrophin gene, but the nature of autosomal forms is unclear. A recently recognized form of dilated CMP, arrhythmogenic CMP/right ventricular dysplasia (ARVD) is linked to two actinin gene loci on chromosomes 1 and 14. Genomic studies of CMP provided a basis for a new stage of "genetic cardiology", genetic mapping, which at present includes the quest of candidate genes for many other human cardiovascular diseases. |
