Journal of Muscle Research and Cell Motility

, Volume 33, Issue 1, pp 75–80

How do MYBPC3 mutations cause hypertrophic cardiomyopathy?

Authors

    • NHLIImperial College London
  • O’Neal Copeland
    • NHLIImperial College London
  • Katja Gehmlich
    • Department of Cardiovascular MedicineUniversity of Oxford
  • Saskia Schlossarek
    • Cardiovascular Research CentreUniversity Medical Center Hamburg-Eppendorf
  • Lucie Carrrier
    • Cardiovascular Research CentreUniversity Medical Center Hamburg-Eppendorf
Review

DOI: 10.1007/s10974-011-9268-3

Cite this article as:
Marston, S., Copeland, O., Gehmlich, K. et al. J Muscle Res Cell Motil (2012) 33: 75. doi:10.1007/s10974-011-9268-3

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.

Keywords

MYBPC3MyBP-CHypertrophic cardiomyopathyHaploinsufficiencyCa2+-regulationNonsense mediated RNA decayUbiquitin-proteasome system

Copyright information

© Springer Science+Business Media B.V. 2011