A novel mutation in the SCN5A gene is associated with Brugada syndrome

Dong Jik Shin, Eunmin Kim, Sang Bum Park, Won Cheoul Jang, Yoonsun Bae, Jihye Han, Yangsoo Jang, Boyoung Joung, Moon Hyoung Lee, Sung Soon Kim, Hai Huang, Mohamed Chahine, Sungjoo Kim Yoon

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Brugada syndrome (BS) is an inherited cardiac disorder associated with a high risk of sudden cardiac death and is caused by mutations in the SCN5A gene encoding the cardiac sodium channel α-subunit (Nav1.5). The aim of this study was to identify the genetic cause of familial BS and characterize the electrophysiological properties of a novel SCN5A mutation (W1191X). Four families and one patient with BS were screened for SCN5A mutations by PCR and direct sequencing. Wild-type (WT) and mutant Nav1.5 channels were expressed in tsA201 cells, and the sodium currents (INa) were analyzed using the whole-cell patch-clamp technique. A novel mutation, W1191X, was identified in a family with BS. Expression of the WT or the mutant channel (Nav1.5/W1191X) co-transfected with the β1-subunit in tsA201 cells resulted in a loss of function of Nav1.5 channels. While voltage-clamp recordings of the WT channel showed a distinct acceleration of Nav1.5 activation and fast inactivation kinetics, the Nav1.5/W1191X mutant failed to generate any currents. Co-expression of the WT channel and the mutant channel resulted in a 50% reduction in INa. No effect on activation and inactivation were observed with this heterozygous expression. The W1191X mutation is associated with BS and resulted in the loss of function of the cardiac sodium channel.

Original languageEnglish
Pages (from-to)716-724
Number of pages9
JournalLife Sciences
Volume80
Issue number8
DOIs
Publication statusPublished - 2007 Jan 30

Fingerprint

Brugada Syndrome
Sodium Channels
Clamping devices
Genes
Chemical activation
Mutation
Gene encoding
Sodium
Kinetics
Electric potential
Sudden Cardiac Death
Patch-Clamp Techniques
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Shin, D. J., Kim, E., Park, S. B., Jang, W. C., Bae, Y., Han, J., ... Yoon, S. K. (2007). A novel mutation in the SCN5A gene is associated with Brugada syndrome. Life Sciences, 80(8), 716-724. https://doi.org/10.1016/j.lfs.2006.10.025
Shin, Dong Jik ; Kim, Eunmin ; Park, Sang Bum ; Jang, Won Cheoul ; Bae, Yoonsun ; Han, Jihye ; Jang, Yangsoo ; Joung, Boyoung ; Lee, Moon Hyoung ; Kim, Sung Soon ; Huang, Hai ; Chahine, Mohamed ; Yoon, Sungjoo Kim. / A novel mutation in the SCN5A gene is associated with Brugada syndrome. In: Life Sciences. 2007 ; Vol. 80, No. 8. pp. 716-724.
@article{518869b0047e4235aca650d7f4c3ff91,
title = "A novel mutation in the SCN5A gene is associated with Brugada syndrome",
abstract = "Brugada syndrome (BS) is an inherited cardiac disorder associated with a high risk of sudden cardiac death and is caused by mutations in the SCN5A gene encoding the cardiac sodium channel α-subunit (Nav1.5). The aim of this study was to identify the genetic cause of familial BS and characterize the electrophysiological properties of a novel SCN5A mutation (W1191X). Four families and one patient with BS were screened for SCN5A mutations by PCR and direct sequencing. Wild-type (WT) and mutant Nav1.5 channels were expressed in tsA201 cells, and the sodium currents (INa) were analyzed using the whole-cell patch-clamp technique. A novel mutation, W1191X, was identified in a family with BS. Expression of the WT or the mutant channel (Nav1.5/W1191X) co-transfected with the β1-subunit in tsA201 cells resulted in a loss of function of Nav1.5 channels. While voltage-clamp recordings of the WT channel showed a distinct acceleration of Nav1.5 activation and fast inactivation kinetics, the Nav1.5/W1191X mutant failed to generate any currents. Co-expression of the WT channel and the mutant channel resulted in a 50{\%} reduction in INa. No effect on activation and inactivation were observed with this heterozygous expression. The W1191X mutation is associated with BS and resulted in the loss of function of the cardiac sodium channel.",
author = "Shin, {Dong Jik} and Eunmin Kim and Park, {Sang Bum} and Jang, {Won Cheoul} and Yoonsun Bae and Jihye Han and Yangsoo Jang and Boyoung Joung and Lee, {Moon Hyoung} and Kim, {Sung Soon} and Hai Huang and Mohamed Chahine and Yoon, {Sungjoo Kim}",
year = "2007",
month = "1",
day = "30",
doi = "10.1016/j.lfs.2006.10.025",
language = "English",
volume = "80",
pages = "716--724",
journal = "Life Sciences",
issn = "0024-3205",
publisher = "Elsevier Inc.",
number = "8",

}

Shin, DJ, Kim, E, Park, SB, Jang, WC, Bae, Y, Han, J, Jang, Y, Joung, B, Lee, MH, Kim, SS, Huang, H, Chahine, M & Yoon, SK 2007, 'A novel mutation in the SCN5A gene is associated with Brugada syndrome', Life Sciences, vol. 80, no. 8, pp. 716-724. https://doi.org/10.1016/j.lfs.2006.10.025

A novel mutation in the SCN5A gene is associated with Brugada syndrome. / Shin, Dong Jik; Kim, Eunmin; Park, Sang Bum; Jang, Won Cheoul; Bae, Yoonsun; Han, Jihye; Jang, Yangsoo; Joung, Boyoung; Lee, Moon Hyoung; Kim, Sung Soon; Huang, Hai; Chahine, Mohamed; Yoon, Sungjoo Kim.

In: Life Sciences, Vol. 80, No. 8, 30.01.2007, p. 716-724.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A novel mutation in the SCN5A gene is associated with Brugada syndrome

AU - Shin, Dong Jik

AU - Kim, Eunmin

AU - Park, Sang Bum

AU - Jang, Won Cheoul

AU - Bae, Yoonsun

AU - Han, Jihye

AU - Jang, Yangsoo

AU - Joung, Boyoung

AU - Lee, Moon Hyoung

AU - Kim, Sung Soon

AU - Huang, Hai

AU - Chahine, Mohamed

AU - Yoon, Sungjoo Kim

PY - 2007/1/30

Y1 - 2007/1/30

N2 - Brugada syndrome (BS) is an inherited cardiac disorder associated with a high risk of sudden cardiac death and is caused by mutations in the SCN5A gene encoding the cardiac sodium channel α-subunit (Nav1.5). The aim of this study was to identify the genetic cause of familial BS and characterize the electrophysiological properties of a novel SCN5A mutation (W1191X). Four families and one patient with BS were screened for SCN5A mutations by PCR and direct sequencing. Wild-type (WT) and mutant Nav1.5 channels were expressed in tsA201 cells, and the sodium currents (INa) were analyzed using the whole-cell patch-clamp technique. A novel mutation, W1191X, was identified in a family with BS. Expression of the WT or the mutant channel (Nav1.5/W1191X) co-transfected with the β1-subunit in tsA201 cells resulted in a loss of function of Nav1.5 channels. While voltage-clamp recordings of the WT channel showed a distinct acceleration of Nav1.5 activation and fast inactivation kinetics, the Nav1.5/W1191X mutant failed to generate any currents. Co-expression of the WT channel and the mutant channel resulted in a 50% reduction in INa. No effect on activation and inactivation were observed with this heterozygous expression. The W1191X mutation is associated with BS and resulted in the loss of function of the cardiac sodium channel.

AB - Brugada syndrome (BS) is an inherited cardiac disorder associated with a high risk of sudden cardiac death and is caused by mutations in the SCN5A gene encoding the cardiac sodium channel α-subunit (Nav1.5). The aim of this study was to identify the genetic cause of familial BS and characterize the electrophysiological properties of a novel SCN5A mutation (W1191X). Four families and one patient with BS were screened for SCN5A mutations by PCR and direct sequencing. Wild-type (WT) and mutant Nav1.5 channels were expressed in tsA201 cells, and the sodium currents (INa) were analyzed using the whole-cell patch-clamp technique. A novel mutation, W1191X, was identified in a family with BS. Expression of the WT or the mutant channel (Nav1.5/W1191X) co-transfected with the β1-subunit in tsA201 cells resulted in a loss of function of Nav1.5 channels. While voltage-clamp recordings of the WT channel showed a distinct acceleration of Nav1.5 activation and fast inactivation kinetics, the Nav1.5/W1191X mutant failed to generate any currents. Co-expression of the WT channel and the mutant channel resulted in a 50% reduction in INa. No effect on activation and inactivation were observed with this heterozygous expression. The W1191X mutation is associated with BS and resulted in the loss of function of the cardiac sodium channel.

UR - http://www.scopus.com/inward/record.url?scp=33846195842&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846195842&partnerID=8YFLogxK

U2 - 10.1016/j.lfs.2006.10.025

DO - 10.1016/j.lfs.2006.10.025

M3 - Article

C2 - 17141278

AN - SCOPUS:33846195842

VL - 80

SP - 716

EP - 724

JO - Life Sciences

JF - Life Sciences

SN - 0024-3205

IS - 8

ER -

Shin DJ, Kim E, Park SB, Jang WC, Bae Y, Han J et al. A novel mutation in the SCN5A gene is associated with Brugada syndrome. Life Sciences. 2007 Jan 30;80(8):716-724. https://doi.org/10.1016/j.lfs.2006.10.025