Genetic analysis of the cardiac sodium channel gene SCN5A in Koreans with Brugada syndrome.
The SCN5A gene encodes the alpha subunit of the human cardiac voltage-gated sodium channel. Mutations in SCN5A are responsible for Brugada syndrome, an inherited cardiac disease that leads to idiopathic ventricular fibrillation (IVF) and sudden death. In this study, we screened nine individuals from a single family and 12 sporadic patients who were clinically diagnosed with Brugada syndrome. Using PCR-SSCP, DHPLC, and DNA sequencing analysis, we identified a novel single missense mutation associated with Brugada syndrome in the family and detected a C5607T polymorphism in Korean subjects. A single nucleotide substitution of G to A at nucleotide position 3934 changed the coding sense of exon 21 of the SCN5A from glycine to serine (G1262S) in segment 2 of domain III (DIII-S2). Four individuals in the family carried the identical mutation in the SCN5A gene, but none of the 12 sporadic patients did. This mutation was not found in 150 unrelated normal individuals. This finding is the first report of a novel mutation in SCN5A associated with Brugada syndrome in Koreans.
Shin
Dong-Jik
DJ
Research Institute of Molecular Genetics, Catholic Research Institutes of Medical Sciences, Seoul, 137-040, South Korea.
Jang
Yangsoo
Y
Cardiovascular Genome Center, Yonsei University Medical Center, Seoul, South Korea.
Park
Hyun-Young
HY
Cardiovascular Genome Center, Yonsei University Medical Center, Seoul, South Korea.
Lee
Jong Eun
JE
DNA Link, Inc, Seoul, South Korea.
Yang
Keumjin
K
Research Institute of Molecular Genetics, Catholic Research Institutes of Medical Sciences, Seoul, 137-040, South Korea.
Kim
Eunmin
E
Research Institute of Molecular Genetics, Catholic Research Institutes of Medical Sciences, Seoul, 137-040, South Korea.
Bae
Yoonjung
Y
Research Institute of Molecular Genetics, Catholic Research Institutes of Medical Sciences, Seoul, 137-040, South Korea.
Kim
Jongmin
J
Research Institute of Molecular Genetics, Catholic Research Institutes of Medical Sciences, Seoul, 137-040, South Korea.
Kim
Jeongki
J
Research Institute of Molecular Genetics, Catholic Research Institutes of Medical Sciences, Seoul, 137-040, South Korea.
Kim
Sung Soon
SS
Department of Cardiology, Yonsei Cardiovascular Center, Seoul, South Korea.
Lee
Moon Hyoung
MH
Department of Cardiology, Yonsei Cardiovascular Center, Seoul, South Korea.
Chahine
Mohamed
M
Laval Hospital Research Centre and Department of Medicine, Laval University, Sainte-Foy, Quebec, Canada.
Yoon
Sungjoo Kim
SK
Research Institute of Molecular Genetics, Catholic Research Institutes of Medical Sciences, Seoul, 137-040, South Korea. sjkyoon@catholic.ac.kr.
D001483:Base Sequence; D002037:Bundle-Branch Block / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D006801:Humans; D007723:Korea; D008297:Male; D062554:NAV1.5 Voltage-Gated Sodium Channel; D015222:Sodium Channels / Q000235:genetics*
D017931:DNA Primers; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels