Calcium dysregulation underlies phenotypic diversity in LQT2: Insights from induced pluripotent stem cell-derived cardiomyocytes of a KCNH2 p.Y427H family trio

BACKGROUND Congenital long QT syndrome (LQTS) is an inherited arrhythmia linked to a high risk of sudden cardiac death. LQTS type 2 is mainly caused by KCNH2 mutations. Even among carriers of the same pathogenic KCNH2 variant, clinical manifestations and disease severity vary, with the underlying mechanisms remaining unclear. AIM To investigate mechanisms underlying variable clinical severity among carriers of the same KCNH2 mutation using patient-specific induced pluripotent stem cell (iPSC)-de