A novel myosin heavy chain 7 mutation (E848G) identified in a familial cardiomyopathy was studied in patient-specific induced pluripotent stem cell-derived cardiomyocytes. The cardiomyopathic human induced pluripotent stem cell-derived cardiomyocytes exhibited reduced contractile function as single cells and engineered heart tissues, and genome-edited isogenic cells confirmed the pathogenic nature of the E848G mutation. Reduced contractility may result from impaired interaction between myosin heavy chain 7 and cardiac myosin binding protein C.
Keywords: Ad-GFP, green fluorescent protein–encoding adenovirus; DCM, dilated cardiomyopathy; EHT, engineered heart tissue; FCM, familial cardiomyopathy; HCM, hypertrophic cardiomyopathy; KO, knockout; MOI, multiplicity of infections; MYH, myosin heavy chain; WT, wild-type; cMyBP-C, cardiac myosin-binding protein C; disease-modeling; engineered heart tissue; genetic cardiomyopathy; hiPSC-CM, human induced pluripotent stem cell–derived cardiomyocyte; iPSC-CM, induced pluripotent stem cell–derived cardiomyocyte; induced pluripotent stem cells.