How do MYBPC3 mutations cause hypertrophic cardiomyopathy?

Journal article

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.

Authors: Marston, S; Copeland, O; Gehmlich, K; Schlossarek, S; Carrier, L

• Publication status: Published
• Journal: Journal of muscle research and cell motility
• Volume: 33
• Issue: 1
• Pages: 75-80
• Publication date: 2012-05-01
• DOI: 10.1007/s10974-011-9268-3
• EISSN: 1573-2657
• ISSN: 0142-4319
• Language: English
• Keywords: Cardiomyopathy, Hypertrophic; Frameshift Mutation; RNA Splicing; Calcium; Carrier Proteins; Myocardium; Codon, Nonsense; Haploinsufficiency; Nonsense Mediated mRNA Decay; Peptide Chain Termination, Translational; Animals; RNA, Messenger; Exons; Humans