Whole-exome sequencing identifies a novel mutation (R367G) in SCN5A to be associated with familial cardiac conduction disease

Cardiac conduction disease is a primary cause of sudden cardiac death. Sodium voltage-gated channel-a subunit 5 (SCN5A) mutations have been reported to underlie a variety of inherited arrhythmias. Numerous disease-causing mutations of SCN5A have been identified in patients with >= 10 different conditions, including type 3 long-QT syndrome and Brugada syndrome. The present study investigated a family with a history of arrhythmia, with the proband having a history of arrhythmia and syncope. Whole-exome sequencing was applied in order to detect the disease-causing mutation in this family, and Sanger sequencing was used to confirm the co-segregation among the family members. A missense mutation (c.1099C>G/p.R367G) of SCN5A was identified in the family and was observed to be co-segregated in all affected members of the family. The missense mutation results in a substitution of glycine for arginine, which may affect sodium transmembrane transport. The present study provides an accurate genetic test which may be used in individuals who exhibit no clinical symptoms.