title: Novel SCN5A mutation (Q55X) associated with age-dependent expression of Brugada syndrome presenting as neurally mediated syncope.
abstract: BACKGROUND
  An association between Brugada syndrome and neurally mediated syncope has been described. Although mutations in SCN5A have been identified in Brugada syndrome, the genetic link between Brugada syndrome and neurally mediated syncope has not been determined.
  
  
  OBJECTIVE
  The purpose of the study was to clinically and genetically characterize a man with recurrent syncope that originally was diagnosed as neurally mediated syncope at age 8 years but subsequently manifested as Brugada syndrome at age 17 years.
  
  
  METHODS
  The proband underwent clinical examination, which included head-up tilt test, sodium channel provocation test, and electrophysiologic study. Genetic screening of SCN5A was performed for the proband and his family members. The biophysical properties of a mutant SCN5A channel in a heterologous expression system were studied using whole-cell, patch clamp technique.
  
  
  RESULTS
  The proband showed positive head-up tilt test, coved-type ST elevation recorded from the third intercostal space, and positive pilsicainide provocation test. Ventricular fibrillation was inducible at programmed electrical stimulation, consistent with characteristics of both Brugada syndrome and neurally mediated syncope. A novel nonsense SCN5A mutation (Q55X) was identified in the proband, his mother, and his asymptomatic brother. The heterologously expressed mutant channel was nonfunctional.
  
  
  CONCLUSIONS
  We genetically determined an SCN5A mutation in a patient showing the combined phenotype of neurally mediated syncope and Brugada syndrome. Neurally mediated syncope and Brugada syndrome may share, at least in part, a common pathophysiologic mechanism.
authors.affiliation: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan. makitan@med.hokudai.ac.jp <makitan@med.hokudai.ac.jp>
authors.forename: Naomasa
authors.initials: N
authors.lastname: Makita
authors.forename: Naokata
authors.initials: N
authors.lastname: Sumitomo
authors.forename: Ichiro
authors.initials: I
authors.lastname: Watanabe
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsutsui
mesh_terms: D000200:Action Potentials; D000293:Adolescent; D000367:Age Factors; D001283:Atrioventricular Node / Q000503:physiopathology; D053840:Brugada Syndrome / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D018389:Codon, Nonsense / Q000235:genetics; D022062:Electrophysiologic Techniques, Cardiac; D005091:Exons / Q000235:genetics; D006801:Humans; D008297:Male; D009124:Muscle Proteins / Q000235:genetics*; D062554:NAV1.5 Voltage-Gated Sodium Channel; D010375:Pedigree; D012849:Sinoatrial Node / Q000503:physiopathology; D015222:Sodium Channels / Q000235:genetics*; D019462:Syncope, Vasovagal / Q000209:etiology*
chemical_list: D018389:Codon, Nonsense; D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels