RESUMO
BACKGROUND: Idiopathic cardiomyopathy was by definition a disease of unknown etiology and there are two major clinical forms, hypertrophic cardiomyopathy and dilated cardiomyopathy. Recent molecular genetic analyses have now revealed that mutations in genes for sarcomere cause hypertrophic cardiomyopathy leading to a hypothesis of hypertrophic cardiomyopathy as sarcomeropathy. On the other hand, mutations in genes for Z-disc component cause dilated cardiomyopathy speculating that dilated cardiomyopathy is cytoskeletopathy at least in part. METHODS: A large panel of Asian patients and families with hypertrophic cardiomyopathy or dilated cardiomyopathy was analyzed for gene abnormalities in all exons and adjacent introns of the known disease-related genes and in a part of several candidates of novel disease-related genes. RESULTS: Mutations in the genes for sarcomere were found in 47% of familial cases and 14% of sporadic cases of hypertrophic cardiomyopathy and there were locus and allelic differences in clinical phenotypes of hypertrophic cardiomyopathy patients. In contrast, only a few patients with dilated cardiomyopathy were identified for mutations in the known disease-causing genes. Mutations in the gene for titin, a giant molecule linking Z-disc with sarcomere components, were found in hypertrophic cardiomyopathy patients. CONCLUSIONS: The molecular etiologies of cardiomyopathy can be identified in about half of hypertrophic cardiomyopathy and a small part of dilated cardiomyopathy, suggesting that there are several novel disease-causing genes. Identification of titin mutation in hypertrophic cardiomyopathy indicate that hypertrophic cardiomyopathy is in part considered as the cytoskeletopathy.
