title: The occurrence of Brugada syndrome and isolated cardiac conductive disease in the same family could be due to a single SCN5A mutation or to the accidental association of both diseases.
abstract: OBJECTIVE
  The distinct cardiac arrhythmia diseases, Brugada syndrome (BS) and isolated cardiac conduction disease (ICCD) are caused by heterozygous mutations in the SCN5A gene. Previous studies have demonstrated an intriguing association between ICCD and BS with the same mutation in the SCN5A gene.
  
  
  RESULTS
  The proband of a multigenerational family presented BS and a familial history of sudden death. We performed clinical evaluations in family members including drug testing and screening for SCN5A mutations. Based on electrocardiogram features, we identified four individuals with BS, two with ICCD and one compatible with both. For five individuals, one with BS and ICCD, three with BS and one with ICCD, we characterized a heterozygous C- to T- mutation at position 4313 (P1438L) in the SCN5A gene. Expression studies of the P1438L mutation showed non-functional channels. The proband's father with the BS phenotype was not a carrier of the new SCN5A mutation.
  
  
  CONCLUSIONS
  We report the case of a family with BS and/or ICCD and describe a novel mutation, the P1438L SCN5A mutation. In this family, the occurrence of BS and ICCD could be due to this single mutation but also to the accidental association of both diseases.
authors.affiliation: INSERM ERI 12, Amiens, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Six
authors.forename: Jean-Sylvain
authors.initials: JS
authors.lastname: Hermida
authors.forename: Hai
authors.initials: H
authors.lastname: Huang
authors.forename: Laetitia
authors.initials: L
authors.lastname: Gouas
authors.forename: Véronique
authors.initials: V
authors.lastname: Fressart
authors.forename: Nawal
authors.initials: N
authors.lastname: Benammar
authors.forename: Bernard
authors.initials: B
authors.lastname: Hainque
authors.forename: Isabelle
authors.initials: I
authors.lastname: Denjoy
authors.forename: Mohamed
authors.initials: M
authors.lastname: Chahine
authors.forename: Pascale
authors.initials: P
authors.lastname: Guicheney
mesh_terms: D000328:Adult; D000368:Aged; D001145:Arrhythmias, Cardiac / Q000235:genetics* / Q000503:physiopathology; D053840:Brugada Syndrome / Q000235:genetics* / Q000503:physiopathology; D004562:Electrocardiography; D005260:Female; D006329:Heart Conduction System / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D062554:NAV1.5 Voltage-Gated Sodium Channel; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels