title: Criteria to predict carriers of a novel SCN5A mutation in a large Portuguese family affected by the Brugada syndrome.
abstract: OBJECTIVE
  Brugada syndrome (BrS) is a life-threatening arrhythmia disorder associated with autosomal-dominant mutations in the SCN5A gene. We aimed to characterize the diagnostic challenges and clinical manifestations of a novel SCN5A mutation associated with BrS.
  
  
  RESULTS
  From a novel SCN5A mutation (c.664C>T; p.Arg222X) identified in a proband with the characteristic electrocardiographic pattern and the history of sudden collapse, 122 family members were studied including 40 carriers of the mutation. The electrocardiographic diagnosis of BrS requires type 1 Brugada electrocardiogram (ECG) pattern in >1 right precordial lead (V1-V3), but recently an isolated lead with coved-type ECG was proposed to be enough for the diagnosis. In this family, these proposed criteria (PC) were more sensitive in detecting mutation carriers than the conventional criteria without repercussion on the specificity. Carriers had, on average, longer P-wave duration, PR, and QRS intervals and higher transmural dispersion of repolarization. The prevalence of late potentials was higher in carriers, and individual signal average ECG (SAECG) parameters (QRSf, LAS, and RMS40) also were related to SCN5A gene mutation. Three non-carriers were found to be affected by BrS, two with a spontaneous type 1 ECG with alternative placement of the precordial electrodes, and one only after the pharmacological provocative test, suggesting that other genes may play a role in the pathophysiology of this disease.
  
  
  CONCLUSIONS
  The PC for BrS diagnosis should be implemented. Some parameters from the spontaneous ECG and the SAECG are more effective tools than the characteristic repolarization pattern to discriminate between carriers of SCN5A mutations.
authors.affiliation: Department of Cardiology, Tondela Viseu Hospital Center, Avenida Rei D Duarte, 3504-509 Viseu, Portugal. luisferreirasantos@gmail.com
authors.forename: Luis Ferreira
authors.initials: LF
authors.lastname: Santos
authors.forename: Bruno
authors.initials: B
authors.lastname: Rodrigues
authors.forename: Davide
authors.initials: D
authors.lastname: Moreira
authors.forename: Emanuel
authors.initials: E
authors.lastname: Correia
authors.forename: Luis
authors.initials: L
authors.lastname: Nunes
authors.forename: Antonio
authors.initials: A
authors.lastname: Costa
authors.forename: Luis
authors.initials: L
authors.lastname: Elvas
authors.forename: Telmo
authors.initials: T
authors.lastname: Pereira
authors.forename: Jose Carlos
authors.initials: JC
authors.lastname: Machado
authors.forename: Sergio
authors.initials: S
authors.lastname: Castedo
authors.forename: Carla
authors.initials: C
authors.lastname: Henriques
authors.forename: Ana
authors.initials: A
authors.lastname: Matos
authors.forename: Jorge Oliveira
authors.initials: JO
authors.lastname: Santos
mesh_terms: D000293:Adolescent; D000328:Adult; D053840:Brugada Syndrome / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D017147:Defibrillators, Implantable; D004562:Electrocardiography / Q000379:methods*; D005192:Family Health; D005260:Female; D006580:Genetic Carrier Screening / Q000379:methods*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D062554:NAV1.5 Voltage-Gated Sodium Channel; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics; D011174:Portugal; D012272:Ribs; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels