Title : A novel SCN 5 A mutation associated with the linker between III - IV domains of Na v 1 . 5 in a neonate with fatal long QT syndrome

A male newborn weighing 2334g was delivered at 37 weeks of gestation by caesarean section because of prenatal ultrasound findings of fetal hydrops with atrioventricualr block, ventriucular tachycardia (VT), and impaired ventricular function. In spite of the intravenous administration of lidocaine, VT continued. He developed poor perfusion and systemic hypotension. After the intravenous administration of amiodarone, VT was terminated. The electrocardiogram revealed an extremely prolonged corrected QT interval (860 ms) with 2:1 atrioventricular block. Unfortunately, he died eighteen hours after birth in spite of the administration of lidocaine, beta-blocker and magnesium. Mutational analysis identified a novel heterozygous de novo mutation (F1486del) in SCN5A. This mutation is associated with the IFM motif in the linker between III-IV domains of Nav1.5, which serves as an inactivation particle binding within the pore of sodium channels. This report demonstrates an interesting relationship between the clinical phenotype and the location of the mutation in long QT syndrome.