Year: 2025
Type: article
Abstract: BACKGROUND: Familial hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease (CVD). Related mutations contributing to hypercontractility and poor relaxation in HCM are not completely understood. PURPOSE: This study aimed to explore and verify a novel variant of cardiac myosin-binding protein C (cMyBP-C, encoded by MYBPC3) in an HCM family. METHODS: Clinical information and cardiac parameters were collected in the pedigree. Genomic DNA was extracted from peripheral blood and second-generation sequencing technology was used to investigate the proband and his family members. Subsequent sequence analysis was performed with DNAMAN software. The cardiac expression levels of MYBPC3 mRNA and cMyBP-C protein were assessed using RT-qPCR and Western blot analysis, respectively. RESULTS: Typical interventricular septal thickening was detected in all four HCM patients without left ventricular outflow tract obstruction. The c.1042_1043insCGGCA mutation in MYBPC3 was verified in the proband and family members. In silico analysis of the mutation revealed that c.1042_1043insCGGCA led to a shift in the sequence of nucleotides, creating a premature stop codon at the new reading frame. RT-qPCR analysis of MYBPC3 mRNA revealed a marked reduction in HCM heart compared to the normal controls (P < 0.05). Consistently, Western blot analysis showed significantly reduced expression of cMyBP-C in the pedigree in comparison with the controls (P < 0.05). CONCLUSION: The novel c.1042_1043insCGGCA MYBPC3 mutation is a genetic basis for HCM due to c-MyBP-C haploinsufficiency.
Source: PLoS ONE
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,382
Funder: Zhejiang Medical Association
OpenAlex ID: W4415525000