期刊
CIRCULATION JOURNAL
卷 77, 期 4, 页码 959-967出版社
JAPANESE CIRCULATION SOC
DOI: 10.1253/circj.CJ-12-0995
关键词
Brugada syndrome; Electrophysiologic study; Genetics; Ion channels; Sodium
资金
- Ministry of Education, Culture, Sports, Science and Technology, Japan
- Ministry of Health, Labour and Welfare, Japan
- Japan Society for the Promotion of Science
- National Research Foundation, Korea
- Tokyo Medical and Dental University
- Medical Research Institute Tokyo Medical and Dental University
- Grants-in-Aid for Scientific Research [24390199, 22390157, 23390209, 24591575, 23659414] Funding Source: KAKEN
Background: Brugada syndrome (BrS) is characterized by specific alterations on ECG in the right precordial leads and associated with ventricular arrhythmia that may manifest as syncope or sudden cardiac death. The major causes of BrS are mutations in SCN5A for a large subunit of the sodium channel, Nav1.5, but a mutation in SCN3B for a small subunit of sodium channel, Nav beta 3, has been recently reported in an American patient. Methods and Results: A total of 181 unrelated BrS patients, 178 Japanese and 3 Koreans, who had no mutations in SCN5A, were examined for mutations in SCN3B by direct sequencing of all exons and adjacent introns. A mutation, Val110lle, was identified in 3 of 178 (1.7%) Japanese patients, but was not found in 480 Japanese controls. The SCN3B mutation impaired the cytoplasmic trafficking of Nav1.5, the cell surface expression of which was decreased in transfected cells. Whole-cell patch clamp recordings of the transfected cells revealed that the sodium currents were significantly reduced by the SCN3B mutation. Conclusions: The Val110lle mutation of SCN3B is a relatively common cause of SCN5A-negative BrS in Japan, which has a reduced sodium current because of the loss of cell surface expression of Nav1.5. (Circ J 2013; 77: 959-967)
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