A consistent arrhythmogenic trait in Brugada syndrome cellular phenotype.

Global cellular electrophysiological phenotype was then evaluated with action potential (AP) recordings, but no AP basal parameters specifically segregated BrS hiPSC-CMs, and spontaneous beating frequencies did not differ between all cell lines (Figure S4). Brugada syndrome (BrS) is an inherited arrhythmic disease predisposing to sudden cardiac death (SCD), characterized by a typical electrocardiogram pattern that includes a J point elevation with a coved type ST segment.1 BrS is a complex genetic disease in which ~20% of patients carry rare variants in I SCN5A i gene, whereas the others remain genetically unresolved.2 Despite this genetic complexity, we hypothesize that a common cellular phenotypic trait is at the root of this specific BrS ECG pattern. Importantly, the expression of I SCN5A i , the main BrS culprit gene identified to date,4 remained unchanged, excluding I SCN5A i expression levels as a hallmark for BrS hiPSC-CM phenotype. Early afterdepolarizations (EADs) were observed in 39-70% of all six BrS ventricular-like hiPSC-CMs versus only in 4% and 4.7% of Ctrl and non-BrS hiPSC-CMs, respectively (Figure 3B, Figure S5). [Extracted from the article]