Molecular genetics of dilated cardiomyopathies.

Abstract

The application of molecular genetics in cardiology is currently producing important results in the study of the pathogenetic mechanisms underlying cardiomyopathies. Recent clinical surveys have indicated that genetic factors play a major pathogenetic role in idiopathic dilated cardiomyopathy (IDC). Familial IDC is frequent (20-30%) and is probably a heterogeneous entity, as suggested by the clinical variability and the different pattern of inheritance in the affected families. Molecular genetic studies have demonstrated the existence of heterogeneity also at the genetic level. In a series of families with X-linked IDC, the disease gene has been identified as the dystrophin gene. In familial right ventricular cardiomyopathy (or right ventricular dysplasia), a new nosological entity characterized by isolated right ventricular involvement that can mimic IDC, the disease gene has been localized in the long arm of chromosome 14. In families with matrilineal transmission, the cardiomyopathy could be linked to mitochondrial DNA alterations. Autosomal dominant familial IDC, considered to be the most frequent form, is currently under active investigation. Our preliminary data have excluded a large series of candidate genes, among which are the cardiac beta-myosin heavy chain and several other genes encoding for cardiac contractile proteins, genes of the HLA region, and about 60 genes involved in the immune regulation.