BACKGROUND: Brugada syndrome is a form of idiopathic ventricular fibrillation 
characterized by right bundle-branch block pattern and ST elevation in the right 
precordial leads of the ECG. The SCN5A gene encodes the alpha-subunit of the 
human heart sodium channel, which plays a critical role in cardiac excitability, 
and mutations of SCN5A could underlie Brugada syndrome.
METHODS AND RESULTS: To detect mutations of SCN5A, DNA samples from 12 Japanese 
patients with Brugada syndrome were analyzed using direct sequencing. Two 
patients had novel mutations, G292S and S835L, but no other mutations of SCN5A 
were detected in the remaining patients. The first mutation, G292S, was 
identified adjacent to the pore-lining region between the DIS5 and DIS6 
transmembrane segments of SCN5A, and the second mutation, S835L, was in the 
intracellular loop connecting the DIIS4 to DIIS5. Both mutations were not 
detected in 100 unrelated control subjects.
CONCLUSION: Two novel SCN5A mutations have been found in Japanese patients with 
Brugada syndrome.