Hostname: page-component-cd9895bd7-gxg78 Total loading time: 0 Render date: 2024-12-25T04:24:00.307Z Has data issue: false hasContentIssue false
  • English
  • Français

Whole-exome sequencing identifies a Novel SCN5A mutation (C335R) in a Chinese family with arrhythmia

Published online by Cambridge University Press:  06 February 2018

Hao Huang ,
Dong-Bo Ding ,
Liang-Liang Fan ,
Jie-Yuan Jin ,
Jing-Jing Li ,
Shuai Guo ,
Ya-qin Chen  and
Rong Xiang
Hao Huang
Affiliation:
School of Life Sciences, Central South University, Changsha, China
Dong-Bo Ding
Affiliation:
School of Life Sciences, Central South University, Changsha, China
Liang-Liang Fan
Affiliation:
School of Life Sciences, Central South University, Changsha, China
Jie-Yuan Jin
Affiliation:
School of Life Sciences, Central South University, Changsha, China
Jing-Jing Li
Affiliation:
School of Life Sciences, Central South University, Changsha, China
Shuai Guo
Affiliation:
School of Life Sciences, Central South University, Changsha, China
Ya-qin Chen
Affiliation:
Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha, China
Rong Xiang*
Affiliation:
School of Life Sciences, Central South University, Changsha, China Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha, China
*
Author for correspondence: Rong Xiang, PhD, Department of Cell Biology, School of Life Sciences, Central South University, Changsha 410013, China. Tel: +86 731 82650230; Fax: +86 731 82650230; E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

SCN5A encodes sodium-channel α-subunit Nav1.5. The mutations of SCN5A can lead to hereditary cardiac arrhythmias such as the long-QT syndrome type 3 and Brugada syndrome. Here we sought to identify novel mutations in a family with arrhythmia.

Methods

Genomic DNA was isolated from blood of the proband, who was diagnosed with atrial flutter. Illumina Hiseq 2000 whole-exome sequencing was performed and an arrhythmia-related gene-filtering strategy was used to analyse the pathogenic genes. Sanger sequencing was applied to verify the mutation co-segregated in the family.

Results and conclusions

A novel missense mutation in SCN5A (C335R) was identified, and this mutation co-segregated within the affected family members. This missense mutation was predicted to result in amplitude reduction in peak Na+ current, further leading to channel protein dysfunction. Our study expands the spectrum of SCN5A mutations and contributes to genetic counselling of families with arrhythmia.

Keywords

SCN5Amissensearrhythmiaatrial flutterwhole-exome sequencing
Type
Original Articles
Information
Cardiology in the Young , Volume 28 , Issue 5 , May 2018 , pp. 688 - 691
Check for updates
Copyright
© Cambridge University Press 2018 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

*

Hao Huang and Dong-bo Ding contributed equally to this work.

References

1. Kwon, CH, Kim, SH. Intraoperative management of critical arrhythmia. Korean J Anesthesiol 2017; 70: 120–126.Google Scholar
2. Veerman, CC, Wilde, AA, Lodder, EM. The cardiac sodium channel gene SCN5A and its gene product NaV1.5: role in physiology and pathophysiology. Gene 2015; 573: 177–187.Google Scholar
3. Vohra, J. Diagnosis and management of Brugada syndrome. Heart Lung Circ 2011; 20: 751–756.Google Scholar
4. Tan, HL, Bink-Boelkens, MT, Bezzina, CR, et al. A sodium-channel mutation causes isolated cardiac conduction disease. Nature 2001; 409: 1043–1047.Google Scholar
5. Hothi, SS, Ara, F, Timperley, J. P. Y1449C SCN5A mutation associated with overlap disorder comprising conduction disease, Brugada syndrome, and atrial flutter. J Cardiovasc Electrophysiol 2015; 26: 93–97.Google Scholar
6. Hassink, RJ, Breur, JM, Loh, P. Fever-induced atrial flutter associated with SCN5A mutation – a first report on successful catheter ablation in a very young child. Int J Cardiol 2014; 171: e31–e34.Google Scholar
7. Tan, ZP, Xie, L, Deng, Y, et al. Whole-exome sequencing identifies Y1495X of SCN5A to be associated with familia conduction disease and sudden death. Sci Rep 2014; 4: 5616.Google Scholar
8. Neu, A, Eiselt, M, Paul, M, et al. A homozygous SCN5A mutation in a severe, recessive type of cardiac conduction disease. Hum Mutat 2010; 31: E1609–E1621.Google Scholar
9. Xiang, R, Fan, LL, Huang, H, et al. A novel mutation of GATA4 (K319E) is responsible for familial atrial septal defect and pulmonary valve stenosis. Gene 2014; 534: 320–323.Google Scholar
10. Cordeiro, JM, Barajas-Martinez, H, Hong, K, et al. Compound heterozygous mutations P336L and I1660V in the human cardiac sodium channel associated with the Brugada syndrome. Circulation 2006; 114: 2026–2033.Google Scholar
11. Remme, CA, Wilde, AA, Bezzina, CR. Cardiac sodium channel overlap syndromes: different faces of SCN5A mutations. Trends Cardiovasc Med 2008; 18: 78–87.Google Scholar
12. Gourraud, JB, Barc, J, Thollet, A, Le Marec, H, Probst, V. Brugada syndrome: diagnosis, risk stratification and management. Arch Cardiovasc Dis 2017; 110: 188–195.Google Scholar
13. Churko, JM, Mantalas, GL, Snyder, MP, Wu, JC. Overview of high throughput sequencing technologies to elucidate molecular pathways in cardiovascular diseases. Circ Res 2013; 112: 1613–1623.CrossRefGoogle ScholarPubMed
14. Mizusawa, Y. Recent advances in genetic testing and counseling for inherited arrhythmias. J Arrhythm 2016; 32: 389–397.Google Scholar
15. Song, W, Shou, W. Cardiac sodium channel Nav1.5 mutations and cardiac arrhythmia. Pediatr Cardiol 2012; 33: 943–949.Google Scholar
Supplementary material: File

Huang et al. supplementary material

Table S1

Download Huang et al. supplementary material(File)
File 17.1 KB