Nelson A Rodríguez, Nihir Patel, Rafael Dariolli, Simon Ng, Angelika G Aleman, Jingqi Q X Gong, Hung-Mo Lin, Matthew Rodríguez, Rebecca Josowitz, Katia Sol-Church, Karen W Gripp, Xianming Lin, Soomin C Song, Glenn I Fishman, Eric A Sobie, Bruce D Gelb
BACKGROUND: Germline HRAS gain-of-function pathogenic variants cause Costello syndrome (CS). During early childhood, 50% of patients develop multifocal atrial tachycardia, a treatment-resistant tachyarrhythmia of unknown pathogenesis. This study investigated how overactive HRAS activity triggers arrhythmogenesis in atrial-like cardiomyocytes (ACMs) derived from human-induced pluripotent stem cells bearing CS-associated HRAS variants. METHODS: HRAS Gly12 mutations were introduced into a human-induced pluripotent stem cells-ACM reporter line...
February 28, 2024: Circulation. Arrhythmia and Electrophysiology