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

Zhu,Jian‑Fang; Du,Li‑Li; Tian,Yuan; Du,Yi‑Mei; Zhang,Ling; Zhou,Tao; Tian,Li

doi:10.3892/etm.2015.2361

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
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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
Published online on: March 16, 2015 https://doi.org/10.3892/etm.2015.2361
Pages: 1639-1645
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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