title: Nucleotide changes in the translated region of SCN5A from Japanese patients with Brugada syndrome and control subjects.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacology, Hirosaki University School of Medicine, 5 Zaifu-cho Hirosaki, 036-8562, Aomori, Japan.
authors.forename: Takenori
authors.initials: T
authors.lastname: Takahata
authors.forename: Norio
authors.initials: N
authors.lastname: Yasui-Furukori
authors.forename: Shingo
authors.initials: S
authors.lastname: Sasaki
authors.forename: Tomonori
authors.initials: T
authors.lastname: Igarashi
authors.forename: Ken
authors.initials: K
authors.lastname: Okumura
authors.forename: Akihiro
authors.initials: A
authors.lastname: Munakata
authors.forename: Tomonori
authors.initials: T
authors.lastname: Tateishi
mesh_terms: 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
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; D009711:Nucleotides; C568320:SCN5A protein, human; D015222:Sodium Channels; D004247:DNA