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The SCN5A Mutation A1180V is Associated With Electrocardiographic Features of LQT3

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Abstract

Mutations of the SCN5A gene are associated with several arrhythmic syndromes including the Brugada syndrome, conduction disease, long QT syndrome type 3 (LQT3), atrial fibrillation, and dilated cardiomyopathy. We report LQT3 associated with an A1180V cardiac sodium channel mutation, previously associated with cardiac conduction block, and dilated cardiomyopathy in three generations of a Chinese family. Clinical, electrocardiographic (ECG), and echocardiographic examination was followed by direct sequencing of SCN5A and HERG to screen genomic DNA from blood samples. The proband presented with multiple syncopes from the age of 7 years and was found to share a mutation with two other members of his family. Continuous ECG monitoring after presentation showed prolonged QTc and biphasic T waves, multiple episodes of ventricular tachycardia and torsades de pointes. The other two mutation carriers showed ECG features of LQT3 without clinical symptoms. Transthoracic echocardiography showed normal cardiac structure in all three mutation carriers. This study shows LQT3 features associated with an A1180V cardiac sodium channel mutation, expanding the spectrum of phenotypes resulting from this mutation in which biophysical study has shown a persistent late Na+ current.

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Acknowledgments

This work is supported by a United Kingdom Royal Society–China National Natural Science Foundation of China (NSFC) joint grant; NSFC Grants No. 30371571 and 30672209; China–Canada Joint Health Research Initiative Proposal 81161120549; and the Wellcome Trust, Medical Research Council, and British Heart Foundation. JAF was supported by a David Phillips Fellowship from the Biotechnology and Biological Sciences Research Council, United Kingdom.

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Authors and Affiliations

  1. Department of Paediatrics, Center of Shaanxi Province Children Cardiovascular Disease, The Shaanxi Provincial People’s Hospital, The Third Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China

    Yanmin Zhang

  2. Physiological Laboratory, University of Cambridge, Cambridge, UK

    Yanmin Zhang, Christopher L.-H. Huang & James A. Fraser

  3. Department of Cardiology, Children’s Hospital of Xi’an, Xi’an, Shaanxi, People’s Republic of China

    Juanli Wang, Nan Zhou, Haijian Xing & Lei Wang

  4. Department of Genetics and Biology/Key Laboratory of Environment and Genes Related to Diseases Ministry of Education, Medical School, Xi’an Jiaotong University, Xi’an, People’s Republic of China

    Suer Chang, Chen Huang & Aiqun Ma

  5. Institute of Cardiovascular Science, University of Manchester, Manchester, UK

    Yanmin Zhang & Ming Lei

  6. Department of Biochemistry, University of Cambridge, Cambridge, UK

    Christopher L.-H. Huang

Authors
  1. Yanmin Zhang
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  2. Juanli Wang
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  3. Suer Chang
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  7. Chen Huang
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  9. Christopher L.-H. Huang
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  10. Ming Lei
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  11. James A. Fraser
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Corresponding author

Correspondence to Yanmin Zhang.

Additional information

Yanmin Zhang and Juanli Wang contributed equally to this study.

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Zhang, Y., Wang, J., Chang, S. et al. The SCN5A Mutation A1180V is Associated With Electrocardiographic Features of LQT3. Pediatr Cardiol 35, 295–300 (2014). https://doi.org/10.1007/s00246-013-0773-6

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  • DOI: https://doi.org/10.1007/s00246-013-0773-6

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