Mutations and SNPs of human cardiac sodium channel alpha subunit gene (SCN5A) in Japanese patients with Brugada syndrome

Background: Brugada syndrome is an inherited arrhythmogenic disease characterized by right bundle branch block pattern and ST segment elevation, leading to the change of V1 to V3 on electrocardiogram, and an increased risk of sudden cardiac death resulting from ventricular fibrillation. The sodium channel alpha 5 subunit (SCN5A) gene encodes a cardiac voltage-dependent sodium channel, and SCN5A mutations have been reported in Brugada syndrome. However, single nucleotide polymorphisms (SNPs) and gene mutations have not been well investigated in Japanese patients with Brugada syndrome. Methods and Results: The SCN5A gene was examined in 58 patients by using PCR and the ABI 3130xl sequencer, revealing 17 SNP patterns and 13 mutations. Of the 13 mutations, 8 were missense mutations (with amino acid change), 4 were silent mutations (without amino acid change), and one case was a mutation within the splicing junction. Six of the eight missense mutations were novel mutations. Interestingly, we detected an R1664H mutation, which was identified originally in long QT syndrome. Conclusion: We found 13 mutations of the SCN5A gene in 58 patients with Brugada syndrome. The disease may be attributable to some of the mutations and SNPs