GENOMIC STUDIES OF HEREDITARY CARDIOMYOPA THIES

Cardiomyopathies (CMP) clinically and genetically belong to the hetero geneous group of myocardial diseases. Among them, three major clinical forms (hypertrophic, dilated, and restricted) are distinguished. Gene tic factors play a substantial role in the etiology of dilated and hyp ertrophic C-MP; family cases constitute more than 20% of these forms. Most familial cases of CMP are inherited as an autosomal dominant char acter. 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 th e mitochondrial genome. The nature of several CMP forms was determined and a number of genetic loci for this disease was revealed by modem m ethods of genetic mapping. In familial hypertrophic cardiomyopathy (FH C), 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 o f FHC are associated with mutations in the mitochondrial tRNA genes. L inkage 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 f orms is unclear. A recently recognized form of dilated CMP, arrhythmog enic CMP/right ventricular dysplasia (ARVD) is linked to two actinin g ene loci on chromosomes 1 and 14. Genomic studies of CMP provided a ba sis for a new stage of ''genetic cardiology'', genetic mapping, which at present includes the quest of candidate genes for many other human cardiovascular diseases.