Genetic analysis of Brugada syndrome in Western Japan: two novel mutations.
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.


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.


CONCLUSIONS
Two novel SCN5A mutations have been found in Japanese patients with Brugada syndrome.
Niimura
Hideya
H
Department of Cardiology, Fukuoka University School of Medicine, Japan.
Matsunaga
Akira
A
Kumagai
Koichiro
K
Ohwaki
Kazuo
K
Ogawa
Masahiro
M
Noguchi
Hiroo
H
Yonemura
Kazue
K
Saku
Keijiro
K
D000328:Adult; D000368:Aged; D001483:Base Sequence; D002037:Bundle-Branch Block / Q000235:genetics*; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D020125:Mutation, Missense; D062554:NAV1.5 Voltage-Gated Sodium Channel; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015222:Sodium Channels / Q000737:chemistry / Q000235:genetics*
D062554:NAV1.5 Voltage-Gated Sodium Channel; D011994:Recombinant Proteins; C568320:SCN5A protein, human; D015222:Sodium Channels