Abstract
Recent progress in molecular genetic research has revealed that mutations in components of sarcomere, affecting force generation or force transmission, cause hypertrophic cardiomyopathy (HCM) and/or dilated cardiomyopathy (DCM) at least in a certain percentage of familial cases. Our extensive analyses disease genes identified thus far among HCM and DCM patients have revealed a considerable number of mutations in Japanese and Korean populations. However, mutations have not been identified in many patients whose disease etiology is unknown, suggesting the presence of additional yet undiscovered diseased genes. In our search for mutations in several candidate genes in patient populations without mutations of known disease genes, we have identified several disease-related mutations in Z-disc components such as titin and telethonin in both HCM and DCM patients. Functional analyses of the titin and telethonin mutations have shown opposite functional changes between the HCM-related and DCM-related mutations. The HCM-related mutations increased the binding affinity of Z- disc components, while the OCM-related mutations decreased their affinity. These observations suggest that the titin and telethonin genes are new disease-genes implicated in both HCM and OCM, and that HCM is a disease of stiff sarcomere, whereas DCM may be a disease of loose sarcomere.
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Kimura, A. et al. (2003). Molecular Etiology of Idiopathic Cardiomyopathy. In: Matsumori, A. (eds) Cardiomyopathies and Heart Failure. Developments in Cardiovascular Medicine, vol 248. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9264-2_31
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DOI: https://doi.org/10.1007/978-1-4419-9264-2_31
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