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

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Item Type:	Article
Title:	Novel correlations between the genotype and the phenotype of hypertrophic and dilated cardiomyopathy: results from the German Competence Network Heart Failure
Creators Name:	Waldmueller, S., Erdmann, J., Binner, P., Gelbrich, G., Pankuweit, S., Geier, C., Timmermann, B., Haremza, J., Perrot, A., Scheer, S., Wachter, R., Schulze-Waltrup, N., Dermintzoglou, A., Schoenberger, J., Zeh, W., Jurmann, B., Brodherr, T., Boergel, J., Farr, M., Milting, H., Blankenfeldt, W., Reinhardt, R., Oezcelik, C., Osterziel, K.J., Loeffler, M., Maisch, B., Regitz-Zagrosek, V., Schunkert, H. and Scheffold, T.
Abstract:	Aims: Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) can both be due to mutations in the genes encoding {beta}-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.
Keywords:	Hypertrophic Cardiomyopathy, Dilated Cardiomyopathy, Mutation, Myosin-Binding Protein, Myosin Heavy Chain
Source:	European Journal of Heart Failure
ISSN:	1388-9842
Publisher:	Oxford University Press
Volume:	13
Number:	11
Page Range:	1185-1192
Date:	November 2011
Official Publication:	https://doi.org/10.1093/eurjhf/hfr074
PubMed:	View item in PubMed

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