title: Multiple arrhythmic syndromes in a newborn, owing to a novel mutation in SCN5A.
abstract: BACKGROUND
  Mutations in the SCN5A gene have been linked to Brugada syndrome (BrS), conduction disease, Long QT syndrome (LQT3), atrial fibrillation (AF), and to pre- and neonatal ventricular arrhythmias.
  
  
  OBJECTIVE
  The objective of this study is to characterize a novel mutation in Na(v)1.5 found in a newborn with fetal chaotic atrial tachycardia, post-partum intraventricular conduction delay, and QT interval prolongation.
  
  
  METHODS
  Genomic DNA was isolated and all exons and intron borders of 15 ion-channel genes were sequenced, revealing a novel missense mutation (Q270K) in SCN5A. Na(v)1.5 wild type (WT) and Q270K were expressed in CHO-K1 with and without the Na(v)β1 subunit. Results. Patch-clamp analysis showed ∼40% reduction in peak sodium channel current (I(Na)) density for Q270K compared with WT. Fast and slow decay of I(Na) were significantly slower in Q270K. Steady-state activation and inactivation of Q270K channels were shifted to positive potentials, and window current was increased. The tetrodotoxin-sensitive late I(Na) was increased almost 3-fold compared with WT channels. Ranolazine reduced late I(Na) in WT and Q270K channels, while exerting minimal effects on peak I(Na).
  
  
  CONCLUSIONS
  The Q270K mutation in SCN5A reduces peak I(Na) while augmenting late I(Na), and may thus underlie the development of atrial tachycardia, intraventricular conduction delay, and QT interval prolongation in an infant.
authors: Danish National Research Foundation Centre for Cardiac Arrhythmia, Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark. kirstinec@sund.ku.dk
authors: Kirstine
authors: K
authors: Calloe
authors: Nicole
authors: N
authors: Schmitt
authors: Soren
authors: S
authors: Grubb
authors: Ryan
authors: R
authors: Pfeiffer
authors: Jens-Peter
authors: JP
authors: David
authors: Ronald
authors: R
authors: Kanter
authors: Jonathan M
authors: JM
authors: Cordeiro
authors: Charles
authors: C
authors: Antzelevitch
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000235:genetics*; D016466:CHO Cells; D002461:Cell Line, Transformed; D006224:Cricetinae; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007473:Ion Channels / Q000235:genetics; D008564:Membrane Potentials / Q000235:genetics* / Q000502:physiology; D020125:Mutation, Missense / Q000235:genetics*; D062554:NAV1.5 Voltage-Gated Sodium Channel; D018408:Patch-Clamp Techniques / Q000379:methods; D015222:Sodium Channels / Q000235:genetics*; D013577:Syndrome
chemical_list: D007473:Ion Channels; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels