title: Novel heterozygous mutation c.4282G>T in theSCN5Agene in a family with Brugada syndrome.
abstract: Brugada syndrome (BrS) is a rare, inherited arrhythmia syndrome. The most well-known gene that is responsible for causing BrS isSCN5A, which encodes the human cardiac Na+channel (Nav1.5) α subunit. To date, it has been reported that >100 mutations inSCN5Acan 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 enzymeNsi1, 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.
authors.affiliation: Central Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Jian-Fang
authors.initials: JF
authors.lastname: Zhu
authors.affiliation: Ion Channelopathy Research Center, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: DU
authors.affiliation: Department of Geriatrics and Nursing, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Ion Channelopathy Research Center, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Yi-Mei
authors.initials: YM
authors.lastname: DU
authors.affiliation: Ion Channelopathy Research Center, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: L I
authors.initials: LI
authors.lastname: Tian
keywords: Brugada syndrome; SCN5A; heterozygous mutation