title: Sodium current and potassium transient outward current genes in Brugada syndrome: screening and bioinformatics.
abstract: BACKGROUND
  Brugada syndrome (BrS) is a primary arrhythmia syndrome characterized by the occurrence of malignant ventricular arrhythmias. Previously, the genes SCN1B, SCN3B, MOG1, and KCND3 have been associated with BrS. Recent data from exome screening efforts permit better discrimination between low-frequency genetic variants and true monogenetic disease-causing variants. We aimed to screen the genes SCN1B through SCN4B, MOG1, CAV3, and KCND3 for variations in a population of SCN5A negative Danish and Iranian BrS patients, as well as research prior associations using newly released exome data.
  
  
  METHODS
  Screening of all exons and splice sites was performed using Sanger sequencing. Bioinformatic searches were performed in the Single-nucleotide polymorphism database (build 132) and in the National Heart, Lung, and Blood Institute Grand Opportunity Exome Sequencing Project (ESP) for both previously published variant-BrS associations and newly uncovered variations within the noted genes.
  
  
  RESULTS
  A total of 42 BrS patients were screened, and 2 different nonsynonymous mutations in SCN1Bb (H162P and R214Q) were found in 2 different Danish patients. The variants were not found in 216 Danish controls, but R214Q was present in ESP data (5 of 841 alleles). No other mutations were found. Previously BrS-associated mutations in KNCD3 and SCN3B were also present in ESP data. This was not the case for MOG1, but a nonsense polymorphism was present in 0.5% of alleles.
  
  
  CONCLUSIONS
  Our study supports the association of SCN1Bb with BrS. However, recently released exome data make some of the prior associations of BrS with genes SCN3B, MOG1, and KCND3 less likely.
authors.affiliation: Danish National Research Foundation Centre for Cardiac Arrhythmia, Copenhagen, Denmark. anders@kanten.dk
authors.forename: Anders G
authors.initials: AG
authors.lastname: Holst
authors.forename: Siamak
authors.initials: S
authors.lastname: Saber
authors.forename: Massoud
authors.initials: M
authors.lastname: Houshmand
authors.forename: Elena V
authors.initials: EV
authors.lastname: Zaklyazminskaya
authors.forename: Yinman
authors.initials: Y
authors.lastname: Wang
authors.forename: Henrik Kjærulf
authors.initials: HK
authors.lastname: Jensen
authors.forename: Lena
authors.initials: L
authors.lastname: Refsgaard
authors.forename: Stig
authors.initials: S
authors.lastname: Haunsø
authors.forename: Jesper Hastrup
authors.initials: JH
authors.lastname: Svendsen
authors.forename: Morten S
authors.initials: MS
authors.lastname: Olesen
authors.forename: Jacob
authors.initials: J
authors.lastname: Tfelt-Hansen
mesh_terms: D000328:Adult; D053840:Brugada Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D019295:Computational Biology; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000235:genetics*; D062547:Voltage-Gated Sodium Channel beta-1 Subunit
chemical_list: C470379:SCN1B protein, human; D015222:Sodium Channels; D062547:Voltage-Gated Sodium Channel beta-1 Subunit; D012964:Sodium; D011188:Potassium