Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
May-2015 Volume 9 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
May-2015 Volume 9 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Novel heterozygous mutation c.4282G>T in the SCN5A gene in a family with Brugada syndrome

  • Authors:
    • Jian‑Fang Zhu
    • Li‑Li Du
    • Yuan Tian
    • Yi‑Mei Du
    • Ling Zhang
    • Tao Zhou
    • Li Tian
  • View Affiliations / Copyright

    Affiliations: Central Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Ion Channelopathy Research Center, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Department of Geriatrics and Nursing, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
    Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1639-1645
    |
    Published online on: March 16, 2015
       https://doi.org/10.3892/etm.2015.2361
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Brugada syndrome (BrS) is a rare, inherited arrhythmia syndrome. The most well‑known gene that is responsible for causing BrS is SCN5A, which encodes the human cardiac Na+ channel (Nav1.5) α subunit. To date, it has been reported that >100 mutations in SCN5A can cause BrS. In the present study, a novel BrS‑associated Nav1.5 mutation, A1428S, was identified in a proband who was successfully resuscitated from an episode of sudden collapse during walking. This mutation was further confirmed by polymerase chain reaction (PCR)‑restriction fragment length polymorphism analysis, which showed that the PCR fragment containing the mutation A1428S could be cut by the restriction enzyme Nsi1, yielding two shorter DNA fragments of 329 and 159 bp, which were not present in family members homozygous for the wild‑type (WT) allele. Furthermore, the electrophysiological properties were analyzed by patch clamp technique. Current density was decreased in the A1428S mutant compared that in the WT. However, neither the steady‑state activation or inactivation, nor the recovery from inactivation exhibited changes between the A1428S mutant and the WT. In conclusion, the results of this study are consistent with the hypothesis that a reduction in Nav1.5 channel function is involved in the pathogenesis of BrS. The structural‑functional study of the Nav1.5 channel enhances the present understanding the pathophysiological function of the channel.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Moreau A, Keller DI, Huang H, et al: Mexiletine differentially restores the trafficking defects caused by two brugada syndrome mutations. Front Pharmacol. 3:622012. View Article : Google Scholar : PubMed/NCBI

2 

Brugada P and Brugada J: Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. A multicenter report. J Am Coll Cardiol. 20:1391–1396. 1992. View Article : Google Scholar : PubMed/NCBI

3 

Bhar-Amato J, Nunn L and Lambiase P: A review of the mechanisms of ventricular arrhythmia in brugada syndrome. Indian Pacing Electrophysiol J. 10:410–425. 2010.PubMed/NCBI

4 

Vohra J: Diagnosis and management of Brugada Syndrome. Heart Lung Circ. 20:751–756. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Wilde AA, Antzelevitch C, Borggrefe M, et al: Proposed diagnostic criteria for the Brugada syndrome: consensus report. Circulation. 106:2514–2519. 2002. View Article : Google Scholar : PubMed/NCBI

6 

Antzelevitch C, Brugada P, Borggrefe M, et al: Brugada syndrome: report of the second consensus conference. Heart Rhythm. 2:429–440. 2005. View Article : Google Scholar : PubMed/NCBI

7 

Chen Q, Kirsch GE, Zhang D, et al: Genetic basis and molecular mechanism for idiopathic ventricular fibrillation. Nature. 392:293–296. 1998. View Article : Google Scholar : PubMed/NCBI

8 

Antzelevitch C, Pollevick GD, Cordeiro JM, et al: Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death. Circulation. 115:442–449. 2007. View Article : Google Scholar : PubMed/NCBI

9 

Burashnikov E, Pfeiffer R, Barajas-Martinez H, et al: Mutations in the cardiac L-type calcium channel associated with inherited J-wave syndromes and sudden cardiac death. Heart Rhythm. 7:1872–1882. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Watanabe H, Koopmann TT, Le Scouarnec S, et al: Sodium channel β1 subunit mutations associated with Brugada syndrome and cardiac conduction disease in humans. J Clin Invest. 118:2260–2268. 2008.PubMed/NCBI

11 

Hu D, Barajas-Martínez H, Medeiros-Domingo A, et al: A novel rare variant in SCN1Bb linked to Brugada syndrome and SIDS by combined modulation of Na(v)1.5 and K(v)4.3 channel currents. Heart Rhythm. 9:760–769. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Hu D, Barajas-Martinez H, Burashnikov E, et al: A mutation in the beta 3 subunit of the cardiac sodium channel associated with Brugada ECG phenotype. Circ Cardiovasc Genet. 2:270–278. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Kattygnarath D, Maugenre S, Neyroud N, et al: MOG1: a new susceptibility gene for Brugada syndrome. Circ Cardiovasc Genet. 4:261–268. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Delpón E, Cordeiro JM, Núñez L, et al: Functional effects of KCNE3 mutation and its role in the development of Brugada syndrome. Circ Arrhythm Electrophysiol. 1:209–218. 2008. View Article : Google Scholar : PubMed/NCBI

15 

Giudicessi JR, Ye D, Tester DJ, et al: Transient outward current (I(to)) gain-of-function mutations in the KCND3-encoded Kv4.3 potassium channel and Brugada syndrome. Heart Rhythm. 8:1024–1032. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Medeiros-Domingo A, Tan BH, Crotti L, et al: Gain-of-function mutation S422L in the KCNJ8-encoded cardiac K(ATP) channel Kir6.1 as a pathogenic substrate for J-wave syndromes. Heart Rhythm. 7:1466–1471. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Ueda K, Hirano Y, Higashiuesato Y, et al: Role of HCN4 channel in preventing ventricular arrhythmia. J Hum Genet. 54:115–121. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Schulze-Bahr E, Eckardt L, Breithardt G, et al: Sodium channel gene (SCN5A) mutations in 44 index patients with Brugada syndrome: different incidences in familial and sporadic disease. Hum Mutat. 21:651–652. 2003. View Article : Google Scholar : PubMed/NCBI

19 

Priori SG, Napolitano C, Gasparini M, et al: Clinical and genetic heterogeneity of right bundle branch block and ST-segment elevation syndrome: A prospective evaluation of 52 families. Circulation. 102:2509–2515. 2000. View Article : Google Scholar : PubMed/NCBI

20 

Priori SG, Napolitano C, Gasparini M, et al: Natural history of Brugada syndrome: insights for risk stratification and management. Circulation. 105:1342–1347. 2002. View Article : Google Scholar : PubMed/NCBI

21 

Cai F, Zhu J, Chen W, et al: A novel PAX6 mutation in a large Chinese family with aniridia and congenital cataract. Mol Vis. 16:1141–1145. 2010.PubMed/NCBI

22 

Zhu JF, Liu HH, Zhou T and Tian L: Novel mutation in exon 56 of the dystrophin gene in a child with Duchenne muscular dystrophy. Int J Mol Med. 32:1166–1170. 2013.PubMed/NCBI

23 

Wang Q, Li Z, Shen J and Keating MT: Genomic organization of the human SCN5A gene encoding the cardiac sodium channel. Genomics. 34:9–16. 1996. View Article : Google Scholar : PubMed/NCBI

24 

Wang Q, Liu M, Xu C, et al: Novel CACNA1S mutation causes autosomal dominant hypokalemic periodic paralysis in a Chinese family. J Mol Med (Berl). 83:203–208. 2005. View Article : Google Scholar : PubMed/NCBI

25 

Tfelt-Hansen J, Winkel BG, Grunnet M and Jespersen T: Inherited cardiac diseases caused by mutations in the Nav1.5 sodium channel. J Cardiovasc Electrophysiol. 21:107–115. 2010. View Article : Google Scholar : PubMed/NCBI

26 

Adsit GS, Vaidyanathan R, Galler CM, et al: Channelopathies from mutations in the cardiac sodium channel protein complex. J Mol Cell Cardiol. 61:34–43. 2013. View Article : Google Scholar : PubMed/NCBI

27 

Amin AS, Asghari-Roodsari A and Tan HL: Cardiac sodium channelopathies. Pflugers Arch. 460:223–237. 2010. View Article : Google Scholar : PubMed/NCBI

28 

Shy D, Gillet L and Abriel H: Cardiac sodium channel NaV1.5 distribution in myocytes via interacting proteins: the multiple pool model. Biochim Biophys Acta. 1833:886–894. 2013. View Article : Google Scholar : PubMed/NCBI

29 

Casini S, Tan HL, Demirayak I, et al: Tubulin polymerization modifies cardiac sodium channel expression and gating. Cardiovasc Res. 85:691–700. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Gavillet B, Rougier JS, Domenighetti AA, et al: Cardiac sodium channel Nav1.5 is regulated by a multiprotein complex composed of syntrophins and dystrophin. Circ Res. 99:407–414. 2006. View Article : Google Scholar : PubMed/NCBI

31 

van Hoorn F, Campian ME, Spijkerboer A, et al: SCN5A mutations in Brugada syndrome are associated with increased cardiac dimensions and reduced contractility. PLoS One. 7:e420372012. View Article : Google Scholar : PubMed/NCBI

32 

Crotti L, Marcou CA, Tester DJ, et al: Spectrum and prevalence of mutations involving BrS1-through BrS12-susceptibility genes in a cohort of unrelated patients referred for Brugada syndrome genetic testing; implications for genetic testing. J Am Coll Cardiol. 60:1410–1418. 2012. View Article : Google Scholar : PubMed/NCBI

33 

Motoike HK, Liu H, Glaaser IW, et al: The Na+ channel inactivation gate is a molecular complex: a novel role of the COOH-terminal domain. J Gen Physiol. 123:155–165. 2004. View Article : Google Scholar : PubMed/NCBI

34 

Kass RS: Sodium channel inactivation in heart: a novel role of the carboxy-terminal domain. J Cardiovasc Electrophysiol 17 Suppl. 1:S21–S25. 2006. View Article : Google Scholar

35 

Rivolta I, Abriel H, Tateyama M, et al: Inherited Brugada and long QT-3 syndrome mutations of a single residue of the cardiac sodium channel confer distinct channel and clinical phenotypes. J Biol Chem. 276:30623–30630. 2001. View Article : Google Scholar : PubMed/NCBI

36 

Petitprez S, Jespersen T, Pruvot E, et al: Analyses of a novel SCN5A mutation (C1850S): conduction vs. repolarization disorder hypotheses in the Brugada syndrome. Cardiovasc Res. 78:494–504. 2008. View Article : Google Scholar : PubMed/NCBI

37 

Shirai N, Makita N, Sasaki K, et al: A mutant cardiac sodium channel with multiple biophysical defects associated with overlapping clinical features of Brugada syndrome and cardiac conduction disease. Cardiovasc Res. 53:348–354. 2002. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhu JF, Du LL, Tian Y, Du YM, Zhang L, Zhou T and Tian L: Novel heterozygous mutation c.4282G>T in the SCN5A gene in a family with Brugada syndrome. Exp Ther Med 9: 1639-1645, 2015.
APA
Zhu, J., Du, L., Tian, Y., Du, Y., Zhang, L., Zhou, T., & Tian, L. (2015). Novel heterozygous mutation c.4282G>T in the SCN5A gene in a family with Brugada syndrome. Experimental and Therapeutic Medicine, 9, 1639-1645. https://doi.org/10.3892/etm.2015.2361
MLA
Zhu, J., Du, L., Tian, Y., Du, Y., Zhang, L., Zhou, T., Tian, L."Novel heterozygous mutation c.4282G>T in the SCN5A gene in a family with Brugada syndrome". Experimental and Therapeutic Medicine 9.5 (2015): 1639-1645.
Chicago
Zhu, J., Du, L., Tian, Y., Du, Y., Zhang, L., Zhou, T., Tian, L."Novel heterozygous mutation c.4282G>T in the SCN5A gene in a family with Brugada syndrome". Experimental and Therapeutic Medicine 9, no. 5 (2015): 1639-1645. https://doi.org/10.3892/etm.2015.2361
Copy and paste a formatted citation
x
Spandidos Publications style
Zhu JF, Du LL, Tian Y, Du YM, Zhang L, Zhou T and Tian L: Novel heterozygous mutation c.4282G>T in the SCN5A gene in a family with Brugada syndrome. Exp Ther Med 9: 1639-1645, 2015.
APA
Zhu, J., Du, L., Tian, Y., Du, Y., Zhang, L., Zhou, T., & Tian, L. (2015). Novel heterozygous mutation c.4282G>T in the SCN5A gene in a family with Brugada syndrome. Experimental and Therapeutic Medicine, 9, 1639-1645. https://doi.org/10.3892/etm.2015.2361
MLA
Zhu, J., Du, L., Tian, Y., Du, Y., Zhang, L., Zhou, T., Tian, L."Novel heterozygous mutation c.4282G>T in the SCN5A gene in a family with Brugada syndrome". Experimental and Therapeutic Medicine 9.5 (2015): 1639-1645.
Chicago
Zhu, J., Du, L., Tian, Y., Du, Y., Zhang, L., Zhou, T., Tian, L."Novel heterozygous mutation c.4282G>T in the SCN5A gene in a family with Brugada syndrome". Experimental and Therapeutic Medicine 9, no. 5 (2015): 1639-1645. https://doi.org/10.3892/etm.2015.2361
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team