Novel SCN3B mutation associated with brugada syndrome affects intracellular trafficking and function of Nav1.5.
Circ J
; 77(4): 959-67, 2013.
Article
em En
| MEDLINE
| ID: mdl-23257389
ABSTRACT
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, Navß3, has been recently reported in an American patient. METHODS ANDRESULTS:
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, Val110Ile, 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 Val110Ile 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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Mutação de Sentido Incorreto
/
Síndrome de Brugada
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Canal de Sódio Disparado por Voltagem NAV1.5
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Subunidade beta-3 do Canal de Sódio Disparado por Voltagem
Tipo de estudo:
Clinical_trials
/
Risk_factors_studies
Limite:
Adolescent
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Adult
/
Aged
/
Animals
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Child
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Female
/
Humans
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Male
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Middle aged
País/Região como assunto:
Asia
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article