Key result
Mutations in sMyBP-C and fMyBP-C paralogs linked to inherited skeletal muscle diseases like distal arthrogryposis.
Why the study?
Although the physiology of various skeletal muscle diseases is defined, the molecular mechanisms underlying the pathological regulation of distal arthrogryposes remain to be elucidated.
The review provides a comprehensive overview of the etiology of genetic muscle disorders induced by mutations in skeletal MyBP-C paralogs, emphasizing their critical role in muscle contractility.
MyBP-C mutations merit inclusion in skeletal myopathy genetic panels; leaves open mechanistic and therapeutic validation.
Skeletal muscle, a highly complex muscle type in the eukaryotic system, is characterized by different muscle subtypes and functions associated with specific myosin isoforms. As a result, skeletal muscle is the target of numerous diseases, including distal arthrogryposes (DAs). Clinically, DAs are a distinct disorder characterized by variation in the presence of contractures in two or more distal limb joints without neurological issues. DAs are inherited, and up to 40% of patients with this condition have mutations in genes that encode sarcomeric protein, including myosin heavy chains, troponins, and tropomyosin, as well as myosin binding protein-C (MYBPC). Our research group and others are actively studying the specific role of MYBPC in skeletal muscles. The MYBPC family of proteins plays a critical role in the contraction of striated muscles. More specifically, three paralogs of the MYBPC gene exist, and these are named after their predominant expression in slow-skeletal, fast-skeletal, and cardiac muscle as sMyBP-C, fMyBP-C, and cMyBP-C, respectively, and encoded by the MYBPC1, MYBPC2, and MYBPC3 genes, respectively. Although the physiology of various types of skeletal muscle diseases is well defined, the molecular mechanism underlying the pathological regulation of DAs remains to be elucidated. In this review article, we aim to highlight recent discoveries involving the role of skeletal muscle-specific sMyBP-C and fMyBP-C as well as their expression profile, localization in the sarcomere, and potential role(s) in regulating muscle contractility. Thus, this review provides an overall summary of MYBPC skeletal paralogs, their potential roles in skeletal muscle function, and future research directions.
No takes yet. Share an insight, caveat, or question.
Song et al. (2023) conducted a review in Genetic muscle disorders (Distal arthrogryposis, Cardiomyopathies). Mutations in skeletal muscle-specific slow and fast myosin binding protein-C (sMyBP-C and fMyBP-C) paralogs are associated with inherited skeletal muscle diseases such as distal arthrogryposis.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: