Dear Editor,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.The SQTS is characterized by a shortening of the corrected QT (QTc) interval, which has been linked to sudden cardiac death. 1,2 Implantable cardioverter-defibrillator therapy is associated with numerous complications. 3 Therefore, drug therapy is important to optimize the treatment of SQTS patients. Recently published data have reported that hydroquinidine is effective in prolonging the QTc interval in SQTS patients. Notably, data have shown that hydroquinidine might exert different effects depending on the genetic variant and/or SQTS form. 4,5 Based on the limited evidence of the clear role of variants in calcium channel subunits in SQTS and the absence of alternative therapies in this rare cohort, 6 we aimed to use cardiomyocytes from induced pluripotent stem cells (hiPSC-CMs) derived from a SQTS5-patient overlapped with BrS carrying a variant in CACNB2 to study the significance of the variant for the clinical phenotype by combining gene editing and electrophysiological analysis in order to identify possible effective drugs for the disease. HiPSC-CMs offered advantages over other models to model channelopathies in the dish. 7,8 For this study, human iPSC lines from one SQTS patient, from two healthy donors, and two Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 gene-edited hiPSC lines were used (Figure S1A,B). TheThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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