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 con- duction 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 chan- nel was searched for mutation identification. The proband manifested sinus node dysfunction, ven- tricular 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 sequen- cing. 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 HEK293-r cells transfected with wild-type or mutant channels. The HEK293T cells trans- fected with plasmid pcDNA3.1-N1380del-SCN5A had no detectable sodium current. Overall, N1380del mutation of SCN5A gene leads to toss of function of sodium channel. N1380del is a pathogenetic mutation which can cause cardiac conduction defect and ventricular tachycardia.