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Molecular Etiology of Idiopathic Cardiomyopathy

Identification of Novel Disease Genes in Hypertrophic Cardiomyopathy and Dilated Cardiomyopathy
  • Akinori Kimura
  • Takeharu Hayashil
  • Manatsu Itoh-Satohl
  • Takuro Arimura
  • Won-Ha Lee
  • Su Yeoun Lee
  • Jeong-Euy Park
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 248)

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.

Keywords

Dilate Cardiomyopathy Disease Gene Hypertrophic Cardiomyopathy Molecular Etiology Regulatory Light Chain Phosphorylation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Akinori Kimura
    • 1
  • Takeharu Hayashil
    • 1
  • Manatsu Itoh-Satohl
    • 1
  • Takuro Arimura
    • 1
  • Won-Ha Lee
    • 2
  • Su Yeoun Lee
    • 2
  • Jeong-Euy Park
    • 2
  1. 1.Department of Molecular Pathogenesis, Medical Research InstituteTokyo Medical and Dental UniversityTokyoJapan
  2. 2.Department of Cardiovascular MedicineSamsung Medical Center, Sungkyunkwan University School of MedicineSeoulKorea

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