We found that 5 out of 102 (4.9%) athletes carried mutations: a heterozygous MYH7Glu935Lys mutation, a heterozygous MYBPC3 Arg160Trp mutation and another heterozygous MYBPC3 Thr1046Met mutation, all of which had been reported as HCM-associated mutations, in 1, 2 and 2 subjects, respectively.
This period of hypertrophically silent HCM also coincided with the years in which most sudden cardiac deaths occurred, particularly in male R92W(TNNT2) carriers.
Here, we used denaturing high-performance liquid chromatography followed by bidirectional sequencing to screen the coding regions of MYH7 and MYBPC3 in a cohort (n = 125) of Italian patients presenting with HCM.
These results suggested that MYH7 and MYBPC3 were the predominant genes responsible for HCM, and TNNT2 mutation less proportionally contributed to Chinese HCM.
Thirty-eight HCM index patients (mean age 60±16 years) underwent systematic mutation screening of eight sarcomeric genes: β-myosin heavy chain (MYH7), myosin-binding protein C (MYBPC3), troponin T (TNNT2), troponin I (TNNI3), myosin ventricular regulatory light chain 2 (MYL2), myosin ventricular essential light chain 1 (MYL3), α-tropomyosin (TPM1), and cardiac α-actin (ACTC), using direct DNA sequencing.
About 130 consecutive patients diagnosed with HCM or DCM (69 with HCM and 61 with DCM) attending the cardiology clinic of Post Graduate Institute of Medical Education and Research were screened for mutations in the MYH7 gene.
In this first expression study in human HCM tissue, increased myofilament protein levels in patients with either MYBPC3- or MYH7-mediated HCM suggest a poison peptide mechanism.
The HCM patients with MYH7 mutations more often had a family history of HCM (43% vs. 29%, p = 0.006), but there was no difference in family history of sudden death (16% vs. 14%, p = NS).
As the first report of feline HCM caused by a variant in MYH7, this study also emphasises this gene as a candidate gene for future studies in cats and highlights the similarity between human and feline HCM.
We designed morpholino antisense oligonucleotides targeting the exon 13 splice donor site in the zebrafish cardiac troponin T (tnnt2) gene, in order to precisely recapitulate a human TNNT2 mutation that causes hypertrophic cardiomyopathy (HCM).
An induced pluripotent stem cell (iPSC) line was generated from peripheral blood mononuclear cells obtained from the whole blood of a 38-year-old female patient with HCM in which genetic testing identified the well-known pathogenic p.Arg403Gln mutation in myosin heavy chain 7. iPSCs express pluripotency markers, demonstrate trilineage differentiation capacity, and display a normal 46,XX female karyotype.
We have previously generated transgenic Sprague-Dawley rats overexpressing a truncated cardiac troponin T (DEL-TNT) molecule, displaying typical features of HCM such as diastolic dysfunction and an increased susceptibility to ventricular arrhythmias.
Likely pathogenic variants were found in three ARVC cases (12%) in PKP2, DSC2 or DSP, two DCM cases (20%) in MYH7, and four HCM cases (27%) in MYBPC3 (3) or MYH7 (1).
Conclusion These results confirm the genetic heterogeneity of NCCM and suggest that the molecular classification of cardiomyopathies includes an MYH7-associated spectrum of NCCM with HCM, RCM, and DCM.
Seven single nucleotide polymorphisms and haplotypes in MYBPH were investigated for hypertrophy modifying effects in 388 individuals (27 families), in which three unique South African HCM-causing founder mutations (p.R403W and pA797T in β-myosin heavy chain gene (MYH7) and p.R92W in the cardiac troponin T gene (TNNT2)) segregate.