A cardiac myosin binding protein C mutation in the Maine Coon cat with familial hypertrophic cardiomyopathy

Hum Mol Genet. 2005 Dec 1;14(23):3587-93. doi: 10.1093/hmg/ddi386. Epub 2005 Oct 19.


Hypertrophic cardiomyopathy (HCM) is one of the most common causes of sudden cardiac death in young adults and is a familial disease in at least 60% of cases. Causative mutations have been identified in several sarcomeric genes, including the myosin binding protein C (MYBPC3) gene. Although numerous causative mutations have been identified, the pathogenetic process is still poorly understood. A large animal model of familial HCM in the cat has been identified and may be used for additional study. As the first spontaneous large animal model of this familial disease, feline familial HCM provides a valuable model for investigators to evaluate pathophysiologic processes and therapeutic (pharmacologic or genetic) manipulations. The MYBPC3 gene was chosen as a candidate gene in this model after identifying a reduction in the protein in myocardium from affected cats in comparison to control cats (P<0.001). DNA sequencing was performed and sequence alterations were evaluated for evidence that they changed the amino acid produced, that the amino acid was conserved and that the protein structure was altered. We identified a single base pair change (G to C) in the feline MYBPC3 gene in affected cats that computationally alters the protein conformation of this gene and results in sarcomeric disorganization. We have identified a causative mutation in the feline MYBPC3 gene that results in the development of familial HCM. This is the first report of a spontaneous mutation causing HCM in a non-human species. It should provide a valuable model for evaluating pathophysiologic processes and therapeutic manipulations.

MeSH terms

  • Amino Acid Substitution
  • Animals
  • Cardiomyopathy, Hypertrophic / genetics*
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cats*
  • Disease Models, Animal*
  • Genotype
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism
  • Point Mutation*
  • RNA, Messenger / metabolism
  • Sarcomeres / metabolism


  • Carrier Proteins
  • Muscle Proteins
  • RNA, Messenger
  • myosin-binding protein C