Here, we investigate MYBPC3 complete deletion as a disease mechanism in HCM by analyzing two unrelated patients with confirmed diagnosis of HCM that tested negative by Sanger sequencing analysis.
This study aimed to explore novel genotype-phenotype correlations in HCM patients with the variants in ACTC1 and myosin-binding protein (MYBPC3) genes in three unrelated Chinese families.
Sequencing of the coding regions of MYBPC3 and MYH7 revealed 21 variants, of which the MYH7 c.5647G>A (p.(Glu1883Lys)) variant was further analysed, because its orthologous variant had already been reported in a human patient with HCM, but with limited causal evidence.
We used wild-type, heterozygous and homozygous hearts (n = 56) from a Mybpc3-targeted knock-out HCM mouse model and imaged the 3D micro-structure by high-resolution episcopic microscopy.
We will summarize recent technological advances and their implication as gene therapy options in HCM with a special focus on treating MYBPC3 mutations and its potential for being a successful bench to bedside example.
Myocardial deoxygenation during stress is observed in MYBPC3HCM patients, even in the presence of normal LV diastolic function, LV global longitudinal strain, and LV wall thickness.
A custom next-generation sequencing (NGS) technology for the HCM panel allowed us to identify compound heterozygous mutations in the MYBPC3 gene, confirming NGS as a molecular diagnostic tool.
Our aim is to characterize predicted protein-truncating variants (PTVs) in MYBPC3, the gene most commonly associated with hypertrophic cardiomyopathy (HCM), found in a series of autopsied HCM cases after sudden unexpected cardiac death.
SarcTrack analysis of hiPSC-CMs carrying a heterozygous truncation variant in the myosin-binding protein C ( MYBPC3) gene, which causes hypertrophic cardiomyopathy, recapitulated seminal disease phenotypes including cardiac hypercontractility and diminished relaxation, abnormalities that normalized with MYK-461 treatment.
Here we compared the effect of phosphomimetic (D282) and wild-type (S282) cMyBP-C gene transfer on the HCM phenotype of engineered heart tissues (EHTs) generated from a mouse model carrying a Mybpc3 mutation (KI).
We studied 140 carriers (G+) of the TPM1-Asp175Asn or MYBPC3-Gln1061X pathogenic variants for HCM: The G+/LVH+ group (n = 98) consisted of mutation carriers with LVH and the G+/LVH- group (n = 42) without LVH.
The mRNA expression levels of MYBPC3 were significantly reduced in mutant iPSC-CMs, but the protein levels were comparable among isogenic iPSC-CMs, suggesting that haploinsufficiency of MYBPC3 does not contribute to the pathogenesis of HCM in vitro.
Generation of an induced pluripotent stem cell line from a hypertrophic cardiomyopathy patient with a pathogenic myosin binding protein C (MYBPC3) p.Arg502Trp mutation.
Twelve HCM patients were included (six had no sarcomere mutations (HCM<sub>smn</sub>) and served as the control group and six harbored mutations in the MYBPC3 gene (MYBPC3<sub>mut</sub>).