Further assessment of the pathogenic nature of a genome-edited isogenic line carrying a known pathogenic MYL3 mutation, MYL3<sub>(170C>G)</sub>, and a carrier-specific iPSC-CMs line, carrying a MYBPC3<sub>(961G>A)</sub> HCM variant, demonstrated the ability of this combined platform to provide both pathogenic and benign assessments.
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.
Increased amount of interstitial fibrosis predicts ventricular arrhythmias, and is associated with reduced myocardial septal function in patients with obstructive hypertrophic cardiomyopathy.
Furthering the link between the sarcomere and primary cardiomyopathies: restrictive cardiomyopathy associated with multiple mutations in genes previously associated with hypertrophic or dilated cardiomyopathy.
Myosin light chain 3 gene (MYL3) mutation was associated with late-onset HCM with relatively poor prognosis; 1 sudden cardiac death and 2 cases of heart failure with atrial fibrillation occurred among 12 subjects with this mutation.
Diagnostic yield, interpretation, and clinical utility of mutation screening of sarcomere encoding genes in Danish hypertrophic cardiomyopathy patients and relatives.
Pathogenic mutations (single nucleotide substitutions) in MYH7, MYBPC3, TNNI3, and MYL3 (six known and six novel) were identified in 60% (10/17) of familial HCM and 10% of sporadic cases (2/21).