Open AccessGenetic, clinical, molecular, and pathogenic aspects of the South Asian–specific polymorphic MYBPC3Δ25bp variant
Author(s) -
Arif Mohammed,
Pooneh Nabavizadeh,
Taejeong Song,
Darshini Desai,
Rohit Singh,
Sholeh Bazrafshan,
Mohit Kumar,
Yigang Wang,
Richard J. Gilbert,
Perundurai S. Dhandapany,
Richard C. Becker,
Evangelia G. Kranias,
Sakthivel Sadayappan
Publication year - 2020
Publication title -
biophysical reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.766
H-Index - 39
eISSN - 1867-2469
pISSN - 1867-2450
DOI - 10.1007/s12551-020-00725-1
Subject(s) - hypertrophic cardiomyopathy , cardiomyopathy , disease , genetics , medicine , genetic testing , myh7 , heart failure , biology , sudden cardiac death , bioinformatics , gene , gene isoform
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 Δ25bp ) 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 Δ25bp 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 Δ25bp variant. An emphasis is to review the latest techniques currently applied to explore the MYBPC3 Δ25bp pathogenesis and to provide a foundation for developing new diagnostic strategies and advances in therapeutics.