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How do MYBPC3 mutations cause hypertrophic cardiomyopathy?

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An Erratum to this article was published on 09 December 2011

Abstract

It is well established that MYBPC3 mutations are the most common cause of hypertrophic cardiomyopathy, accounting for about half of identified mutations. However, when compared with mutations in other myofibrillar proteins that cause hypertrophic cardiomyopathy, MYBPC3 mutations seem to be the odd one out. The most striking characteristic of HCM mutations in MYBPC3 is that many are within introns and are predicted to cause aberrant splicing leading to a frameshift and a premature chain termination, yet the truncated peptides have never been identified in human heart tissue carrying these mutations. Instead of expression of a poison peptide we consistently observe haploinsufficiency of MyBP-C in MYBPC3 mutant human heart muscle. In this review we investigate the mechanism for MyBP-C haploinsufficiency and consider how this haploinsufficiency could cause hypertrophic cardiomyopathy.

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Acknowledgments

We acknowledge support from the 7th Framework Program of the European Union (“BIG-HEART,” grant agreement 241577).

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Authors and Affiliations

  1. NHLI, Imperial College London, London, UK

    Steven Marston & O’Neal Copeland

  2. Department of Cardiovascular Medicine, University of Oxford, Oxford, UK

    Katja Gehmlich

  3. Cardiovascular Research Centre, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Saskia Schlossarek & Lucie Carrrier

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  1. Steven Marston
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  2. O’Neal Copeland
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  3. Katja Gehmlich
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  4. Saskia Schlossarek
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  5. Lucie Carrrier
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Correspondence to Steven Marston.

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Marston, S., Copeland, O., Gehmlich, K. et al. How do MYBPC3 mutations cause hypertrophic cardiomyopathy?. J Muscle Res Cell Motil 33, 75–80 (2012). https://doi.org/10.1007/s10974-011-9268-3

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  • DOI: https://doi.org/10.1007/s10974-011-9268-3

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