Nucleotide changes in the translated region of SCN5A from Japanese patients with Brugada syndrome and control subjects.
The mutations of the SCN5A gene have been implicated to play a pathogenetic role in Brugada syndrome, which causes ventricular fibrillation. To determine the Brugada-associated mutations in Japanese patients, facilitate pre-symptomatic diagnosis, and allow genotype-phenotype studies, we screened unrelated patients with Brugada syndrome for mutations. DNAs from 6 Japanese patients were obtained and the sequence in the translated region of SCN5A was determined. We could not find the mutations reported previously, but found 17 sites of nucleotide change, consisting of 7 synonymous and 10 non-synonymous nucleotide changes in our patients. Among them, two non-synonymous nucleotide changes (G1663A and G5227A) are specific to our patients and these changes were not found in 53 healthy controls. In 4 patients out of 6, no specific nucleotide change for Brugada syndrome could be detected. Our findings demonstrating no patient-specific change in the translated region of the SCN5A gene among two thirds of the small number of patients examined here imply that another gene other than the SCN5A may be associated with this disease, supporting previous investigations in Japan and other countries.
Takahata
Takenori
T
Department of Clinical Pharmacology, Hirosaki University School of Medicine, 5 Zaifu-cho Hirosaki, 036-8562, Aomori, Japan.
Yasui-Furukori
Norio
N
Sasaki
Shingo
S
Igarashi
Tomonori
T
Okumura
Ken
K
Munakata
Akihiro
A
Tateishi
Tomonori
T
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA / Q000032:analysis; D004252:DNA Mutational Analysis; D004562:Electrocardiography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D062554:NAV1.5 Voltage-Gated Sodium Channel; D009710:Nucleotide Mapping; D009711:Nucleotides / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis / Q000235:genetics*; D015222:Sodium Channels / Q000235:genetics*; D013577:Syndrome; D014693:Ventricular Fibrillation / Q000235:genetics* / Q000503:physiopathology
D062554:NAV1.5 Voltage-Gated Sodium Channel; D009711:Nucleotides; C568320:SCN5A protein, human; D015222:Sodium Channels; D004247:DNA