South Asian-Specific MYBPC3Δ25bp Deletion Carriers Display Hypercontraction and Impaired Diastolic Function Under Exercise Stress

Bazrafshan, Sholeh; Sibilia, Robert; Girgla, Saavia; Viswanathan, Shiv Kumar; Puckelwartz, Megan J.; Sangha, Kiranpal S.; Singh, Rohit; Kakroo, Mashhood; Jandarov, Roman; Harris, David; Rubinstein, Jack; Becker, Richard C.; McNally, Elizabeth M.; Sadayappan, Sakthivel

doi:10.3389/fcvm.2021.766339

Cited by 1 publication

(1 citation statement)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent evidence suggests that asymptomatic carriers of MYBPC3 125bp mutation have a higher risk of left ventricular hypercontraction and diastolic dysfunction during the bicycle stress echocardiogram [ 92 ]. Studies focusing on genetic mutations and clinical correlations in HCM are summarized in Table 1 .…”

Section: From Genetics To Clinical Implicationsmentioning

confidence: 99%

An Update on MYBPC3 Gene Mutation in Hypertrophic Cardiomyopathy

Tudurachi,

Zăvoi,

Leonte

et al. 2023

IJMS

View full text Add to dashboard Cite

Hypertrophic cardiomyopathy (HCM) is the most prevalent genetically inherited cardiomyopathy that follows an autosomal dominant inheritance pattern. The majority of HCM cases can be attributed to mutation of the MYBPC3 gene, which encodes cMyBP-C, a crucial structural protein of the cardiac muscle. The manifestation of HCM’s morphological, histological, and clinical symptoms is subject to the complex interplay of various determinants, including genetic mutation and environmental factors. Approximately half of MYBPC3 mutations give rise to truncated protein products, while the remaining mutations cause insertion/deletion, frameshift, or missense mutations of single amino acids. In addition, the onset of HCM may be attributed to disturbances in the protein and transcript quality control systems, namely, the ubiquitin–proteasome system and nonsense-mediated RNA dysfunctions. The aforementioned genetic modifications, which appear to be associated with unfavorable lifelong outcomes and are largely influenced by the type of mutation, exhibit a unique array of clinical manifestations ranging from asymptomatic to arrhythmic syncope and even sudden cardiac death. Although the current understanding of the MYBPC3 mutation does not comprehensively explain the varied phenotypic manifestations witnessed in patients with HCM, patients with pathogenic MYBPC3 mutations can exhibit an array of clinical manifestations ranging from asymptomatic to advanced heart failure and sudden cardiac death, leading to a higher rate of adverse clinical outcomes. This review focuses on MYBPC3 mutation and its characteristics as a prognostic determinant for disease onset and related clinical consequences in HCM.

show abstract

Section: From Genetics To Clinical Implicationsmentioning

confidence: 99%