title: Brugada syndrome and p.E61X_RANGRF.
abstract: BACKGROUND
  Brugada syndrome is an inherited cardiac condition transmitted with an autosomal dominant pattern which can lead to sudden cardiac death from malignant ventricular arrhythmias. The RANGRF gene has recently been proposed to be associated with Brugada syndrome. This gene encodes the MOG1 protein, a co-factor required for the full functioning of the cardiac sodium channel Nav1.5. The nonsense p.E61X genetic variation in the RANGRF gene has been postulated as responsible for Brugada syndrome although no clear association has been established.
  
  
  METHODS
  We clinically and genetically evaluated a Spanish family diagnosed with Brugada syndrome. A comprehensive genetic analysis of all genes to date responsible for Brugada syndrome was performed in the index case.
  
  
  RESULTS
  The index case was clinically diagnosed with Brugada syndrome after flecainide test. We identified a nonsense variation (p.E61X) in the index case and in other five family members. All of them showed a normal electrocardiogram in basal conditions. Flecainide test unmasked a type 1 Brugada syndrome electrocardiogram only in two of the relatives.
  
  
  CONCLUSIONS
  We suggest that p.E61X_RANGRF is a rare genetic variation with an uncertain role in Brugada Syndrome. Further studies must be performed to elucidate the potential pathogenic role of p.E61X_RANGRF in Brugada Syndrome.
authors.affiliation: Cardiovascular Genetics Center, University of Girona. oscar@brugada.org.
authors.forename: Oscar
authors.initials: O
authors.lastname: Campuzano
authors.forename: Paola
authors.initials: P
authors.lastname: Berne
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Selga
authors.forename: Catarina
authors.initials: C
authors.lastname: Allegue
authors.forename: Anna
authors.initials: A
authors.lastname: Iglesias
authors.forename: Josep
authors.initials: J
authors.lastname: Brugada
authors.forename: Ramon
authors.initials: R
authors.lastname: Brugada
mesh_terms: D000328:Adult; D000368:Aged; D000889:Anti-Arrhythmia Agents; D053840:Brugada Syndrome / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D004562:Electrocardiography; D005260:Female; D005424:Flecainide; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006801:Humans; D008297:Male; D010641:Phenotype; D011237:Predictive Value of Tests; D013030:Spain; D061567:Voltage-Gated Sodium Channel Blockers; D020931:ran GTP-Binding Protein / Q000235:genetics*
chemical_list: D000889:Anti-Arrhythmia Agents; D018389:Codon, Nonsense; D061567:Voltage-Gated Sodium Channel Blockers; C498735:RANGNRF protein, human; D020931:ran GTP-Binding Protein; D005424:Flecainide