Abstract 776: MYBPC3 Mutations in Indian Patients With Hypertrophic Cardiomyopathy

Abstract

Introduction: Hypertrophic cardiomyopathy (HCM), the most common inherited heart disease, is characterized by thickening of the ventricular wall, myocyte disarray, and fibrosis, resulting in impaired cardiac function and leading to adverse ventricular remodeling, heart failure and increased risk for sudden cardiac death. Importantly, mutations in the gene encoding cardiac myosin binding protein-C ( MYBPC3 ), a muscle contractile protein,account for approximately 50% of the reported HCM cases. However, the prevalence of penetrance of MYBPC3 mutations in Indian patients with HCM is yet to be systematically studied. Methods: The Institutional Human Ethics Committee at the University of Puneapproved the present study. HCM patients undergoing treatment in theCardiology Unit of Bharti Hospital, Pune, were identified. With the approval of written informed consent, blood samples were obtained from all patients and their relatives and screened by single-strand conformation polymorphism (SSCP) and direct DNA sequencing, followed by correlation with clinical outcome. Results: Of the 23 probands screened in this study, one, #16, showed a mutation in exon 07 (A/G) at chromosomal position 47370041, causing a protein change at position NP_000247.2:p.S236G, and reported as SNP status ID rs386584787. The mutation was localizedto the immunoglobulin domain of cardiac myosin binding protein-C, causing an amino acid change from serine to glycine with a score of 0.00, as shown by thePolyPhen-2 (Polymorphism Phenotyping v2) tool.G>C transversion of intron variant in exon 21 of MYBPC3 results in a new exon splicing enhancer (ESE) site which may alter splicing. G>A transition at g. 20167 is an intron variant of a previously reported status (rs373904644). This polymorphism results in the creation of an intronic splicingenhancer (ISE) site. The proband had left ventricular wall thickness of 24 mm, ejection fraction of 60 (%), and left ventricular internal diameter of 30 mm, suggesting early onset of HCM. Conclusion: The MYBPC3 mutations might play a key role in thedevelopment of HCM in the Indian population, indicating the soundness of establishing a systematic screening of all HCM patients.