Molecular genetics and pathogenesis of cardiomyopathy

J Hum Genet. 2016 Jan;61(1):41-50. doi: 10.1038/jhg.2015.83. Epub 2015 Jul 16.


Cardiomyopathy is defined as a disease of functional impairment in the cardiac muscle and its etiology includes both extrinsic and intrinsic factors. Cardiomyopathy caused by the intrinsic factors is called as primary cardiomyopathy of which two major clinical phenotypes are hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Genetic approaches have revealed the disease genes for hereditary primary cardiomyopathy and functional studies have demonstrated that characteristic functional alterations induced by the disease-associated mutations are closely related to the clinical types, such that increased and decreased Ca(2+) sensitivities of muscle contraction are associated with HCM and DCM, respectively. In addition, recent studies have suggested that mutations in the Z-disc components found in HCM and DCM may result in increased and decreased stiffness of sarcomere, respectively. Moreover, functional analysis of mutations in the other components of cardiac muscle have suggested that the altered response to metabolic stresses is associated with cardiomyopathy, further indicating the heterogeneity in the etiology and pathogenesis of cardiomyopathy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cardiomyopathies / genetics*
  • Connectin / genetics
  • Contractile Proteins / genetics
  • Cytoskeletal Proteins / genetics
  • Humans
  • Mutation
  • Sarcomeres / genetics


  • Connectin
  • Contractile Proteins
  • Cytoskeletal Proteins
  • TTN protein, human