A nonsense SCN5A mutation associated with brugada-type electrocardiogram and intraventricular conduction defects

Kaveh Samani, Tomohiko Ai, Jeffrey A. Towbin, Ramon Brugada, Mossaab Shuraih, Yutao Xi, Geru Wu, Jie Cheng, Matteo Vatta

Research output: Contribution to journalArticle

2 Scopus citations


Mutations of SCN5A, gene-encoding α-subunit of cardiac sodium channel, can cause mixed phenotypes of Brugada syndrome (BrS) and cardiac conduction diseases (CCD). We have identified a nucleotide change of SCN5A (4178T > G), which results in a nonsense mutation, L1393X, in a 36-year-old Caucasian man who presented with intraventricular conduction delays and BrS-type electrocardiogram change. To study biophysical characteristics of L1393X-SCN5A, electrophysiological and immuno-staining studies were performed using mammalian expression systems. While WT-SCN5A showed significant currents (93.3 ± 10.6 pA/pF; 1 μg plasmid), L1393X (5 μg) did not generate any significant currents in NIH-3T3 cells. The cells cotransfected with WT (0.5 μg) and L1393X (0.5 μg) showed approximately 50% current amplitudes compared to the WT (1 μg). Voltage dependency of a steady-state activation and inactivation was not affected by the cotransfection of L1393X. Immuno-histochemical stainings demonstrated that L1393X proteins were expressed in the plasma membranes. Our study demonstrated that L1393X-SCN5A does not form functional channel proteins, which might account for the patient's mixed phenotypes of BrS and CCD.

Original languageEnglish (US)
Pages (from-to)1231-1236
Number of pages6
JournalPACE - Pacing and Clinical Electrophysiology
Issue number9
StatePublished - Sep 1 2009
Externally publishedYes



  • Basic
  • Clinical
  • Electrophysiology

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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