title: Dynamic change in ST-segment and spontaneous occurrence of ventricular fibrillation in Brugada syndrome with a novel nonsense mutation in the SCN5A gene during long-term follow-up.
abstract: A 67-year-old male underwent genetic testing under the diagnosis of Brugada syndrome because of recurrent ventricular fibrillation with coincident ST-segment elevation in either right precordial, inferior leads or both since the age of 55 years. Screening of gene mutations using denaturing high-performance liquid chromatography (DHPLC) and direct sequencing identified a novel nonsense mutation (R179X) of SCN5A in a heterozygous manner. The functional assay for the identified mutation, using a whole-cell patch clamp in the heterologous expression system, revealed that the nonsense mutation, located in the second transmembrane segment of the first domain (DI-S2) of the alpha-subunit, failed to synthesize the complete structure of the cardiac sodium channel, thus causing the non-functional channel. Coding effects by the gene mutation was altered during the 12-year follow-up, which might affect the clinical features of the patient through the ion channel density in the ventricle, dynamics of repolarization abnormality and conduction disturbance.
authors.affiliation: Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Mihoko
authors.initials: M
authors.lastname: Kawamura
authors.forename: Tomoya
authors.initials: T
authors.lastname: Ozawa
authors.forename: Takenori
authors.initials: T
authors.lastname: Yao
authors.forename: Takashi
authors.initials: T
authors.lastname: Ashihara
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Sugimoto
authors.forename: Takafumi
authors.initials: T
authors.lastname: Yagi
authors.forename: Hideki
authors.initials: H
authors.lastname: Itoh
authors.forename: Makoto
authors.initials: M
authors.lastname: Ito
authors.forename: Takeru
authors.initials: T
authors.lastname: Makiyama
authors.forename: Minoru
authors.initials: M
authors.lastname: Horie
mesh_terms: D053840:Brugada Syndrome / Q000175:diagnosis / Q000235:genetics*; D002478:Cells, Cultured; D018389:Codon, Nonsense; D004562:Electrocardiography; D005192:Family Health; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D062554:NAV1.5 Voltage-Gated Sodium Channel; D017434:Protein Structure, Tertiary; D015222:Sodium Channels / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D014693:Ventricular Fibrillation / Q000175:diagnosis / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels