Deciphering the pathogenic role of a variant with uncertain significance for short QT and Brugada syndromes using gene-edited human-induced pluripotent stem cell-derived cardiomyocytes and preclinical drug screening

In the present study, we show that the Calcium Voltage-Gated Channel Auxiliary Subunit Beta 2 (CACNB2) variant c.1439C>T/p.S480L is linked to the clinical phenotype of short QT syndrome 5 (SQTS5) overlapped with Brugada syndrome (BrS). The PI3K pathway may contribute to the arrhythmogenesis of the disease. PI3K-activator and amiodarone but not sotalol may be effective drugs for treating arrhythmias in SQTS5-patients carrying but not limited to this variant.