Caroline Kinnear, Abdelrahman Said, Guoliang Meng, Yimu Zhao, Erika Y Wang, Naimeh Rafatian, Neha Parmar, Wei Wei, Filio Billia, Craig A Simmons, Milica Radisic, James Ellis, Seema Mital
Pathogenic variants in MYH7 and MYBPC3 account for the majority of hypertrophic cardiomyopathy (HCM). Targeted drugs like myosin ATPase inhibitors have not been evaluated in children. We generate patient and variant-corrected iPSC-cardiomyocytes (CMs) from pediatric HCM patients harboring single variants in MYH7 (V606M; R453C), MYBPC3 (G148R) or digenic variants (MYBPC3 P955fs, TNNI3 A157V). We also generate CMs harboring MYBPC3 mono- and biallelic variants using CRISPR editing of a healthy control. Compared with isogenic and healthy controls, variant-positive CMs show sarcomere disorganization, higher contractility, calcium transients, and ATPase activity...
April 16, 2024: Cell reports medicine