A novel SCN5A mutation associated with idiopathic ventricular fibrillationwithout typical ECG findings of Brugada syndrome

Mutations in the human cardiac Na+ channel alpha subunit gene (SCN5A) are r esponsible for Brugada syndrome, an idiopathic ventricular fibrillation (IV F) subgroup characterized by right bundle branch block and ST elevation on an electrocardiogram (ECC). However, the molecular basis of IVF in subgroup s lacking these ECG findings has not been elucidated. We performed genetic screenings of Japanese IVF patients and found a novel SCN5A missense mutati on (S1710L) in one symptomatic IVF patient that did not exhibit the typical Brugada ECC. Heterologously expressed S1710L channels showed marked accele ration in the current decay together with a large hyperpolarizing shift of steady-state inactivation and depolarizing shift of activation. These findi ngs suggest that SCN5A is one of the responsible genes for IVF patients who do not show typical ECC manifestations of the Brugada syndrome, (C) 2000 F ederation of European Biochemical Societies, Published by Elsevier Science B.V. All rights reserved.