title: Novel SCN3B mutation associated with brugada syndrome affects intracellular trafficking and function of Nav1.5.
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, Navβ3, has been recently reported in an American patient.
  
  
  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, 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.
authors.affiliation: Division of Genetic Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Naohiko
authors.initials: N
authors.lastname: Takahashi
authors.forename: Seiko
authors.initials: S
authors.lastname: Ohno
authors.forename: Harumizu
authors.initials: H
authors.lastname: Sakurada
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Nakamura
authors.forename: Young Keun
authors.initials: YK
authors.lastname: On
authors.forename: Jeong Euy
authors.initials: JE
authors.lastname: Park
authors.forename: Takeru
authors.initials: T
authors.lastname: Makiyama
authors.forename: Minoru
authors.initials: M
authors.lastname: Horie
authors.forename: Takuro
authors.initials: T
authors.lastname: Arimura
authors.forename: Naomasa
authors.initials: N
authors.lastname: Makita
authors.forename: Akinori
authors.initials: A
authors.lastname: Kimura
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D000818:Animals; D044466:Asian People; D053840:Brugada Syndrome / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D002648:Child; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000235:genetics; D062549:Voltage-Gated Sodium Channel beta-3 Subunit / Q000235:genetics* / Q000378:metabolism
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C493324:SCN3B protein, human; C568320:SCN5A protein, human; D062549:Voltage-Gated Sodium Channel beta-3 Subunit