p.N1380del mutation in the pore-forming region of SCN5A gene is associated with cardiac conduction disturbance and ventricular tachycardia.
Cardiac sodium channel plays a key role in the fast depolarization and maintenance of impulse conduction in cardiomyocytes. Mutations of SCN5A gene can lead to many types of arrhythmias. A 14-year-old boy with familial paternal history of sudden unexpected nocturnal death was admitted to hospital with recurrent syncope. A cardiac channelopathy was suspected and a pathogenic ion channel was searched for mutation identification. The proband manifested sinus node dysfunction, ventricular tachycardia, cardiac conduction disturbance involving atrioventricular node and His bundle. The proband and his mother received whole exome sequencing. A heterozygous in-frame deletion N1380del on exon 23 of SCN5A gene locating in a highly conserved pore residue in domain III (S5-S6) was revealed in the proband. The mutation was assessed in other family members by Sanger sequencing. The proband's living uncle and two sisters were asymptomatic mutation carriers with different degrees of cardiac conduction disturbance. Functional analysis was conducted using whole-cell patch clamping in HEK293T cells transfected with wild-type or mutant channels. The HEK293T cells transfected with plasmid pcDNA3.1-N1380del-SCN5A had no detectable sodium current. Overall, N1380del mutation of SCN5A gene leads to loss of function of sodium channel. N1380del is a pathogenetic mutation which can cause cardiac conduction defect and ventricular tachycardia.
Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Zhen
Z
Yang
Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Danbo
D
Lu
Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Lei
L
Zhang
Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Jialu
J
Hu
Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Zhenning
Z
Nie
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai 200031, China.
Chang
C
Xie
Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai 200031, China.
Fang
F
Qiu
WuXi NextCODE Genomics, Shanghai 200131, China.
Hua
H
Cheng
Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Yan
Y
Yan
D000293:Adolescent; D000075224:Cardiac Conduction System Disease / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D005091:Exons; D006801:Humans; D008297:Male; D009154:Mutation; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics*; D010641:Phenotype; D011379:Prognosis; D017180:Tachycardia, Ventricular / Q000235:genetics* / Q000473:pathology / Q000628:therapy
D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human
SCN5A; cardiac conduction disturbance; mutation; ventricular tachycardia