Novel correlations between the genotype and the phenotype of hypertrophic and dilated cardiomyopathy: results from the German Competence Network Heart Failure

Eur J Heart Fail. 2011 Nov;13(11):1185-92. doi: 10.1093/eurjhf/hfr074. Epub 2011 Jul 12.


Aims: Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) can both be due to mutations in the genes encoding β-myosin heavy chain (MYH7) or cardiac myosin-binding protein C (MYBPC3). The aim of the present study was to determine the prevalence and spectrum of mutations in both genes in German HCM and DCM patients and to establish novel genotype-to-phenotype correlations.

Methods and results: Coding exons and intron flanks of the two genes MYH7 and MYBPC3 of 236 patients with HCM and 652 patients with DCM were sequenced by conventional and array-based means. Clinical records were established following standard protocols. Mutations were detected in 41 and 11% of the patients with HCM and DCM, respectively. Differences were observed in the frequency of splice site and frame-shift mutations in the gene MYBPC3, which occurred more frequently (P< 0.02, P< 0.001, respectively) in HCM than in DCM, suggesting that cardiac myosin-binding protein C haploinsufficiency predisposes to hypertrophy rather than to dilation. Additional novel genotype-to-phenotype correlations were found in HCM, among these a link between MYBPC3 mutations and a particularly large thickness of the interventricular septum (P= 0.04 vs. carriers of a mutation in MYH7). Interestingly, this correlation and a link between MYH7 mutations and a higher degree of mitral valve regurgitation held true for both HCM and DCM, indicating that the gene affected by a mutation may determine the magnitude of structural and functional alterations in both HCM and DCM.

Conclusion: A large clinical-genetic study has unravelled novel genotype-to-phenotype correlations in HCM and DCM which warrant future investigation of both the underlying mechanisms and the prognostic use.

Publication types

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

MeSH terms

  • Cardiomyopathy, Dilated / epidemiology
  • Cardiomyopathy, Dilated / genetics*
  • Cardiomyopathy, Hypertrophic / epidemiology
  • Cardiomyopathy, Hypertrophic / genetics*
  • Genetic Predisposition to Disease
  • Humans
  • Mutation
  • Phenotype