Incomplete-penetrant hypertrophic cardiomyopathy <i>MYH7</i> G256E mutation causes hypercontractility and elevated mitochondrial respiration.

ABSTRACT: Determining the pathogenicity of hypertrophic cardiomyopathy-associated mutations in the β-myosin heavy chain (MYH7) can be challenging due to its variable penetrance and clinical severity. This study investigates the early pathogenic effects of the incomplete-penetrant MYH7 G256E mutation on myosin function that may trigger pathogenic adaptations and hypertrophy. We hypothesized that the G256E mutation would alter myosin biomechanical function, leading to changes in cellular functions. We developed a collaborative pipeline to characterize myosin function across protein, myofibril, cell, and tissue levels to determine the multiscale effects on structure-function of the contractile apparatus and its implications for gene regulation and metabolic state. The G256E mutation disru

SUBMITTER: Lee S 

PROVIDER: S-EPMC11087781 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature