Whole-exome sequencing identifies a Novel SCN5A mutation (C335R) in a Chinese family with arrhythmia

BACKGROUND: SCN5A encodes sodium-channel α-subunit Nav1.5. The mutations of SCN5A can lead to hereditary cardiac arrhythmias such as the long-QT syndrome type 3 and Brugada syndrome. Here we sought to identify novel mutations in a family with arrhythmia. METHODS: Genomic DNA was isolated from blood of the proband, who was diagnosed with atrial flutter. Illumina Hiseq 2000 whole-exome sequencing was performed and an arrhythmia-related gene-filtering strategy was used to analyse the pathogenic genes. Sanger sequencing was applied to verify the mutation co-segregated in the family.Results and conclusionsA novel missense mutation in SCN5A (C335R) was identified, and this mutation co-segregated within the affected family members. This missense mutation was predicted to result in amplitude reduction in peak Na+ current, further leading to channel protein dysfunction. Our study expands the spectrum of SCN5A mutations and contributes to genetic counselling of families with arrhythmia.