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Research Article: Novel MYBPC Mutations in Indian Population with Cardiomyopathies

Date Published: 2023-09-20

Abstract:
Cardiac Myosin Binding Protein C (MyBP-C_OMIM-), one of the thick filaments exhibited across the C zone of A-bands of sarcomeres, binds ß-myosin (ß-MYH_OMIM-) in thick filaments and titin (TTN_OMIM-) in elastic filaments., It serves as a control that limits cross-bridge interactions between myosin and actin., Phosphorylation of MYBPC modulates contraction and is believed to play both structural and regulatory functions. A total of isoforms of MyBP-C (a cardiac and two skeletal) have been reported, all share a conserved region composed of IgI (immunoglobulin) and FnIII (fibronectin type III) domains. The cardiac isoform cMyBP-C contains a unique IgI domain (C) at the N-terminus and four distinctive phosphorylation sites and an exclusive proline-rich residue insertion at the C domain., Cardiomyopathy (CM), a heart muscle disease, is classified by its morphological features leading to subtypes called hypertrophic (HCM), dilated (DCM), left ventricular noncompaction (LVNC), restrictive (RCM), and arrhythmogenic right ventricular cardiomyopathy (ARVD/C)., The former two (HCM and DCM) are the most frequent forms of cardiomyopathies, usually affecting the cardiac wall thickness, chamber size and ultimately pumping efficiency. Describing features of HCM include a hypertrophied/thickened left ventricle with weakened diastolic relaxation, myocyte disarray, and replacement fibrosis, with an estimated prevalence of in . HCM is known as a “disease of the sarcomere”. Sarcomere consists of thick filaments of myosin and thin filaments of actin, tropomyosin, troponin complex, along with the assembly proteins cardiac myosin binding protein C and titin. To date, hundreds of mutations in sarcomere genes have been reported to cause cardiomyopathies,– most of the mutations (~%) were found in HCM and a few mutations (~–%) were in hereditary DCM. Mutations were predominantly reported in two sarcomere genes: ß-Myosin heavy chain (MYH) and Myosin binding protein C (MYBPC). Defining characteristics of DCM are a left ventricular dilatation, myocardial fibrosis, and myocyte disease, which affect systolic function with an estimated prevalence of in ., Currently, more than genes, TTN, LMNA, DES RBM, etc., along with sarcomere genes were reported to cause familial DCM.,,– The essence of mutation screening in disease genetics mostly relayed on the interpretation of genotype and phenotype correlation. Sometimes the factors that govern the variable phenotypic expressions are largely due to unknown factors like epigenetics, environment, lifestyle, etc., which may also possibly implicate a significant role in disease phenotypes., Mutations in myosin binding protein C (MYBPC) gene, one of the most frequent causes of cardiomyopathies, studied extensively in various other populations–,, but not much studied in the Indian population with cardiomyopathies., Therefore, here, we performed a targeted screening of the MYBPC gene in cardiomyopathy patients against controls (ethnically matched healthy individuals).

Introduction:
Cardiac Myosin Binding Protein C (MyBP-C_OMIM-), one of the thick filaments exhibited across the C zone of A-bands of sarcomeres, binds ß- myosin ( ß-MYH_OMIM-) in thick filaments and titin ( TTN_OMIM-) in elastic filaments. , It serves as a control that limits cross-bridge interactions between myosin and actin. , Phosphorylation of MYBPC modulates contraction and is believed to play both structural and regulatory functions. A total of isoforms of MyBP-C (a cardiac and two skeletal) have been reported, all share a…

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