Genetika dilatační kardiomyopatie a myopatií

Cor Vasa 2003, 44(6):329-332

The genetics of dilated cardiomyopathy and myopathies

Lenka Špinarová^*, †Jiří Toman: I. interní-kardioangiologická klinika, Fakultní nemocnice u sv. Anny a Lékařská fakulta Masarykovy Univerzity, Brno, Česká republika

Dilated cardiomyopathy is a genetically heterogenic disease. In controlled studies, genetic transfer has been demonstrated in 20-25% of patients. The most frequent mutations associated with dilated cardiomyopathy are those with the cytoskeleton and the nuclear membrane while the dominant defects associated with hypertrophic cardiomyopathy are those related to the sarcomere, beta-myosin, and troponin T. Heredity of genetic mutations is autosomal dominant (A/C laminae, actin, desmin), or recessive (sarcoglycans); with dystrophin, emerin and tafazzin, it is bound to chromosome X, mitochondrial defects are rare.
Like Duchenne's muscular dystrophy and Becker's muscular dystrophy, X-linked dilated cardiomyopathy is associated with dystrophin gene mutations.
Limb Girdle Muscular Dystrophy (LGMD) is a highly heterogeneous group of muscular disease characterized primarily by muscular weakness and degradation of the pelvic and shoulder plexus muscles. These conditions may be autosomal dominant (Type 1 LGMD) or autosomal recessive (Type 1, LGMD) hereditary diseases. Type-2 LGMD are divided, depending on the protein involved, into sarcoglycanopathies and non-sarcoglycanopathies. Cardiomyopathy has been reported in patients with alpha-, beta-, and gamma-sarcoglycogan gene mutations.
Emery-Dreifuss muscular dystrophy is a genetically heterogeneous condition characterized by a combination of skeletal and myocardial muscle involvement. It occurs in both X-linked and autosomal dominant forms. Autosomal forms are due to mutations in the A/C lamina gene whilst the X-linked form was associated with mutations in the gene encoding the protein emerin.
Several potential therapeutic options have been proposed in experiment. One includes the possibility of partially making up for the loss of dystrophin by utrophin administration. The reason for this is the observation of several times higher utrophin expression in the muscle fibers of female carriers and patients with dystrophies. Transmission of delta sarcoglycan for substitution on its deletion has also been reported in experiment.