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.
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.
Kawamura
Mihoko
M
Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan.
Ozawa
Tomoya
T
Yao
Takenori
T
Ashihara
Takashi
T
Sugimoto
Yoshihisa
Y
Yagi
Takafumi
T
Itoh
Hideki
H
Ito
Makoto
M
Makiyama
Takeru
T
Horie
Minoru
M
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*
D018389:Codon, Nonsense; D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels