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

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

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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
Volume32
Issue number9
DOIs
StatePublished - Sep 1 2009
Externally publishedYes

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Brugada Syndrome
Nonsense Codon
Electrocardiography
Heart Diseases
Staining and Labeling
Phenotype
NIH 3T3 Cells
Sodium Channels
Proteins
Plasmids
Nucleotides
Cell Membrane
Mutation
Genes

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

A nonsense SCN5A mutation associated with brugada-type electrocardiogram and intraventricular conduction defects. / Samani, Kaveh; Ai, Tomohiko; Towbin, Jeffrey; Brugada, Ramon; Shuraih, Mossaab; Xi, Yutao; Wu, Geru; Cheng, Jie; Vatta, Matteo.

In: PACE - Pacing and Clinical Electrophysiology, Vol. 32, No. 9, 01.09.2009, p. 1231-1236.

Research output: Contribution to journalArticle

Samani, Kaveh ; Ai, Tomohiko ; Towbin, Jeffrey ; Brugada, Ramon ; Shuraih, Mossaab ; Xi, Yutao ; Wu, Geru ; Cheng, Jie ; Vatta, Matteo. / A nonsense SCN5A mutation associated with brugada-type electrocardiogram and intraventricular conduction defects. In: PACE - Pacing and Clinical Electrophysiology. 2009 ; Vol. 32, No. 9. pp. 1231-1236.
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