TitleGenetic, clinical, molecular, and pathogenic aspects of the South Asian-specific polymorphic MYBPC3 variant.
Publication TypeJournal Article
Year of Publication2020
AuthorsArif M, Nabavizadeh P, Song T, Desai D, Singh R, Bazrafshan S, Kumar M, Wang Y, Gilbert RJ, Dhandapany PS, Becker RC, Kranias EG, Sadayappan S
JournalBiophys Rev
Date Published2020 Aug

Hypertrophic cardiomyopathy (HCM) is a cardiac genetic disease characterized by ventricular enlargement, diastolic dysfunction, and increased risk for sudden cardiac death. Sarcomeric genetic defects are the predominant known cause of HCM. In particular, mutations in the myosin-binding protein C gene (MYBPC3) are associated with ~ 40% of all HCM cases in which a genetic basis has been established. A decade ago, our group reported a 25-base pair deletion in intron 32 of MYBPC3 (MYBPC3) that is uniquely prevalent in South Asians and is associated with autosomal dominant cardiomyopathy. Although our studies suggest that this deletion results in left ventricular dysfunction, cardiomyopathies, and heart failure, the precise mechanism by which this variant predisposes to heart disease remains unclear. Increasingly appreciated, however, is the contribution of secondary risk factors, additional mutations, and lifestyle choices in augmenting or modifying the HCM phenotype in MYBPC3 carriers. Therefore, the goal of this review article is to summarize the current research dedicated to understanding the molecular pathophysiology of HCM in South Asians with the MYBPC3 variant. An emphasis is to review the latest techniques currently applied to explore the MYBPC3 pathogenesis and to provide a foundation for developing new diagnostic strategies and advances in therapeutics.

Alternate JournalBiophys Rev
PubMed ID32656747
PubMed Central IDPMC7429610
Grant List19UFEL34380251 / / American Heart Association (US) /
17CCRG33671128 / / American Heart Association (US) /
15CVGPSD27020012 / / American Heart Association /
HL130356 / HL / NHLBI NIH HHS / United States
HL139680 / HL / NHLBI NIH HHS / United States
HL105826 / / National Heart, Lung, and Blood Institute (US) /
AR067279 / AR / NIAMS NIH HHS / United States
19TPA34830084 / / American Historical Association /
HL130356 / HL / NHLBI NIH HHS / United States
HL139680 / HL / NHLBI NIH HHS / United States
AR067279 / AR / NIAMS NIH HHS / United States