Key result
Novel MYBPC3 frameshift mutation linked to late-onset HCM in a four-member family.
Why the study?
Mutations contributing to hypercontractility and poor relaxation in familial hypertrophic cardiomyopathy remain incompletely understood.
Case Report (n=4)
No
A novel c.1042_1043insCGGCA mutation in MYBPC3 was identified as the genetic basis for familial hypertrophic cardiomyopathy, associated with a mild phenotype and delayed onset.
Answers are grounded in this paper and cite their sources.
Supports expanding MYBPC3 variant databases for late-onset HCM; hypothesis-generating and should not yet change practice.
Background Familial hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease. Related mutations contributing to hypercontractility and poor relaxation in HCM have been incompletely understood. The purpose of this study was to explore and verify a novel variant in cardiac myosin-binding protein C3 (MYBPC3) in a HCM family. Methods Clinical information was collected and cardiac evaluation was performed in the pedigree. Second-generation sequencing technology was used to investigate the proband and his family. Computational prediction of mutation effects at genomic level and 3D visualization of the mutated protein were achieved by in silico analysis. Results Typical interventricular septal thickening was detected in all the four HCM patients. A c.1042_1043insCGGCA mutation of MYBPC3 was verified in the proband and family members. Mild phenotype associated with delayed onset and relative favorable prognosis were observed in the pedigree. In silico analysis of the mutation revealed that c.1042_1043insCGGCA led to an early termination of MYBPC protein synthesis at C2 domain, losing the domains that are essential for myosin-and titin-binding. Conclusion The novel c.1042_1043insCGGCA mutation of MYBPC3 was a genetic basis for HCM. Our gene sequence based computational analysis predicted the pathogenicity of the mutation by correlating MYBPC3 genotypes with clinical phenotypes.
No takes yet. Share an insight, caveat, or question.
Zhang et al. (2024) conducted a case report in Hypertrophic Cardiomyopathy (n=4). MYBPC3 c.1042_1043insCGGCA mutation was evaluated on Genetic variant identification and pathogenicity. A novel c.1042_1043insCGGCA frameshift mutation in the MYBPC3 gene was identified as the pathogenic cause of late-onset hypertrophic cardiomyopathy in a four-member family.
Synapse has enriched 8 closely related papers on similar clinical questions. Consider them for comparative context: