The G263X MYBPC3 mutation is a common and low-penetrant mutation for hypertrophic cardiomyopathy in the region of Asturias (Northern Spain)

Abstract

Hypertrophic cardiomyopathy (HCM) is characterised by wide disease manifestations, ranging from severe left ventricular septum (LVS) size and incapacitating symptoms to normal LVS and no symptoms at all. In addition to life style and other non-genetic factors, the phenotype variability could be explained in part by the heterogeneous genetic background of MCH [ 1 Keren A. Syrris P. McKenna W.J. Hypertrophic cardiomyopathy: the genetic determinants of clinical disease expression. Nat Clin Pract Cardiovasc Med. 2008; 5: 158-168 Crossref PubMed Scopus (161) Google Scholar , 2 Bos J.M. Towbin J.A. Ackerman M.J. Diagnostic, prognostic, and therapeutic implications of genetic testing for hypertrophic cardiomyopathy. J Am Coll Cardiol. 2009; 54: 201-211 Abstract Full Text Full Text PDF PubMed Scopus (268) Google Scholar , 3 Richard P. Charron P. Carrier L. et al. Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy. Circulation. 2003; 107: 2227-2232 Crossref PubMed Scopus (983) Google Scholar ]. Moreover, the mutated gene and the type of mutation could also influence disease severity. The myosin binding protein C3 (MYBPC3) is the most frequently mutated gene and has been linked to a delayed expression of HCM. In the other hand, cardiac beta-myosin heavy chain (MYH7) mutations are commonly found among patients with early onset symptoms and severe disease manifestations [ 3 Richard P. Charron P. Carrier L. et al. Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy. Circulation. 2003; 107: 2227-2232 Crossref PubMed Scopus (983) Google Scholar , 4 García-Castro M. Coto E. Reguero J.R. et al. Mutations in sarcomeric genes MYH7, MYBPC3, TNNT2, TNNI3, and TPM1 in patients with hypertrophic cardiomyopathy. Rev Esp Cardiol. 2009; 62: 48-56 Crossref PubMed Scopus (55) Google Scholar ].