Brugada syndrome is an inherited arrhythmia syndrome associated with sudden cardiac death. Na+-current dysfunction is central in Brugada syndrome, but mutations in the cardiac Na+-channel gene SCN5A are present in only20% of probands. Since only a minority of Brugada patients has detectable mutations, we considered alternative disease mechanisms involving a consistent pattern of variations in cardiac electrogenenic processes. We specifically hypothesized that a common pattern of cardiac ion channel and transporter gene-expression might contribute to the pathophysiology of Brugada syndrome by producing a phenotypic background that facilitates expression of characteristic ECG abnormalities and arrhythmogenesis in the context of appropriate genotypic and/or environmental factors. To test this notion, we applied high-throughput real-time PCR, which permits accurate quantification of up to hundreds of transcripts in minute biological samples, to obtained full profiling of ion-channel expression in right-ventricular septal endomyocardial biopsies from 10 patients with Brugada syndrome in comparison with biopsies from 11 non-diseased organ donors, 7 heart transplant recipients, 10 patients with arrhythmogenic right-ventricular cardiomyopathy and 9 with idiopathic right-ventricular outflow-tract tachycardia. Brugada patients showed distinct and reproducible clustering differences versus the two control and two ventricular tachyarrhythmia groups, including14 of 77 genes encoding important ion-channel/ion-transporter subunits. Nav1.5,Kv4.3 andKir3.4 were more weakly-expressed, while Nav2.1 and TWIK1 were more strongly-expressed, in Brugada syndrome. Important differences were also seen in transcripts involved in Ca2+-homeostasis, including stronger expression of RYR2 and NCX1. The molecular profile of five Brugada patients with SCN5A mutations did not differ from Brugada patients without SCN5A mutations. Brugada patients exhibit a common ion-channel molecular expression signature, irrespective of the culprit gene. This finding has potentially important implications for our understanding of the pathophysiology of Brugada syndrome, with possible therapeutic and diagnostic implications.Le texte complet de cet article est disponible en PDF.