REPORT OF A NEW MUTATION (Va1748Leu) ASSOCIATED WITH HYPERTOPHIC MIOCARDIOPATHY LOCATED IN THE C5 DOMAIN OF THE CARDIAC MYOSIN BINDING PROTEIN-C (cMyBP-C)

Hypertophic miocardiopathy (HMC) is a primary hearth disease mainly characterized by left ventricle hypertrophy, its most serious consequence being sudden death. It has been associated to sarcomeric protein mutations, cardiac beta-myosin and the cardiac myosin binding protein-C (cMyBP-C) being the most affected. Since until now, only clinical diagnostic of HCM has been performed in Venezuela, it was decided to study it at the genetic level. In collaboration with the Asociacion Cardiovascular Centro Occidental (ASCARD10), blood samples from clinically diagnosed HCM patients living in Lara state, Venezuela, were analyzed. Following informed consent, genomic DNA was isolated from each patient and control, the exons that conform three of ther genes associated with HCM (MYBPC3, MYHZ MYL2) were amplified by PCR and sequericed to detect possible mutations. A new mutation found: a substitution G>C (Va1748Leu) in exon 24 of the MYBPC3 gene. Utilizing the atomic structure of the central C5 (PDB 1GXE) domain of the human cardiac isoform of cMyBP-C, the mutation was localized in the F chain of the C5 domain of cMyBP-C. This location could specifically affect the establishment of the FG contact, which is considered as the initial step in the C5 domain folding. Therefore, we propose that the alteration of such folding could be associated with HCM, contributing to the observed clinical phenotype.