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.
Our objective was to measure the length of mitral valve leaflets by cardiovascular magnetic resonance (CMR) in subjects with HCM caused by a Finnish founder mutation in the myosin-binding protein C gene (MYBPC3-Q1061X), carriers of the same mutation without left ventricular hypertrophy, as well as in unselected consecutive patients with HCM, and respective controls.
In the nationwide FinHCM Study including 306 Finnish patients with hypertrophic cardiomyopathy (HCM), we have previously identified two founder mutations in the alpha-tropomyosin (TPM1-D175N) and myosin-binding protein C (MYBPC3-Q1061X) genes, accounting for 18% of all cases.Objective.
Four of the nine variants, a nonsense mutation Gln1061X, a splice acceptor mutation (IVS5-2A-->C), a novel substitution in intron 14 (IVS14-13G-->A), and a novel 3-bp deletion in exon 25 (Ex25DeltaLys) were concluded to be disease-causing mutations because they cosegregated with the HCM phenotype or were absent in more than 200 normal chromosomes, or both.
An iPSC line was generated from peripheral blood mononuclear cells obtained from the whole blood of a 58-year-old male with hypertrophic cardiomyopathy who carries the heterozygous pathogenic myosin binding protein C mutation p.Arg502Trp.
Here, we study possible mechanisms of unbinding using steered molecular dynamics simulations for the complex in the wild type, in single mutations (E258K in C1, E441K in C2), as well as in a double mutation (E258K in C1 + E441K in C2), which are associated with severe HCM.
Comparison of echocardiographic and cardiac magnetic resonance imaging in hypertrophic cardiomyopathy sarcomere mutation carriers without left ventricular hypertrophy.
Our objective was to define the primary contractile effect and molecular disease mechanisms of the prevalent cMyBP-C E258KHCM-causing mutation in nonremodeled murine engineered cardiac tissue (mECT).
E258K HCM-causing mutation in cardiac MyBP-C reduces contractile force and accelerates twitch kinetics by disrupting the cMyBP-C and myosin S2 interaction.
Cardiac myosin binding protein-C mutations in families with hypertrophic cardiomyopathy: disease expression in relation to age, gender, and long term outcome.