title: Comprehensive Genetic Characterization of a Spanish Brugada Syndrome Cohort.
abstract: BACKGROUND
  Brugada syndrome (BrS) is a rare genetic cardiac arrhythmia that can lead to sudden cardiac death in patients with a structurally normal heart. Genetic variations in SCN5A can be identified in approximately 20-25% of BrS cases. The aim of our work was to determine the spectrum and prevalence of genetic variations in a Spanish cohort diagnosed with BrS.
  
  
  RESULTS
  We directly sequenced fourteen genes reported to be associated with BrS in 55 unrelated patients clinically diagnosed. Our genetic screening allowed the identification of 61 genetic variants. Of them, 20 potentially pathogenic variations were found in 18 of the 55 patients (32.7% of the patients, 83.3% males). Nineteen of them were located in SCN5A, and had either been previously reported as pathogenic variations or had a potentially pathogenic effect. Regarding the sequencing of the minority genes, we discovered a potentially pathogenic variation in SCN2B that was described to alter sodium current, and one nonsense variant of unknown significance in RANGRF. In addition, we also identified 40 single nucleotide variations which were either synonymous variants (four of them had not been reported yet) or common genetic variants. We next performed MLPA analysis of SCN5A for the 37 patients without an identified genetic variation, and no major rearrangements were detected. Additionally, we show that being at the 30-50 years range or exhibiting symptoms are factors for an increased potentially pathogenic variation discovery yield.
  
  
  CONCLUSIONS
  In summary, the present study is the first comprehensive genetic evaluation of 14 BrS-susceptibility genes and MLPA of SCN5A in a Spanish BrS cohort. The mean pathogenic variation discovery yield is higher than that described for other European BrS cohorts (32.7% vs 20-25%, respectively), and is even higher for patients in the 30-50 years age range.
authors.affiliation: Cardiovascular Genetics Centre, Institut d'Investigació Biomèdica de Girona (IDIBGi), Girona, Spain and Medical School, Universitat de Girona (UdG), Girona, Spain.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Selga
authors.affiliation: Cardiovascular Genetics Centre, Institut d'Investigació Biomèdica de Girona (IDIBGi), Girona, Spain and Medical School, Universitat de Girona (UdG), Girona, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Campuzano
authors.affiliation: Cardiovascular Genetics Centre, Institut d'Investigació Biomèdica de Girona (IDIBGi), Girona, Spain and Medical School, Universitat de Girona (UdG), Girona, Spain.
authors.forename: Mel Lina
authors.initials: ML
authors.lastname: Pinsach-Abuin
authors.affiliation: Cardiovascular Genetics Centre, Institut d'Investigació Biomèdica de Girona (IDIBGi), Girona, Spain and Medical School, Universitat de Girona (UdG), Girona, Spain.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Pérez-Serra
authors.affiliation: Cardiovascular Genetics Centre, Institut d'Investigació Biomèdica de Girona (IDIBGi), Girona, Spain and Medical School, Universitat de Girona (UdG), Girona, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Mademont-Soler
authors.affiliation: Cardiovascular Genetics Centre, Institut d'Investigació Biomèdica de Girona (IDIBGi), Girona, Spain and Medical School, Universitat de Girona (UdG), Girona, Spain.
authors.forename: Helena
authors.initials: H
authors.lastname: Riuró
authors.affiliation: Cardiovascular Genetics Centre, Institut d'Investigació Biomèdica de Girona (IDIBGi), Girona, Spain and Medical School, Universitat de Girona (UdG), Girona, Spain.
authors.forename: Ferran
authors.initials: F
authors.lastname: Picó
authors.affiliation: Cardiovascular Genetics Centre, Institut d'Investigació Biomèdica de Girona (IDIBGi), Girona, Spain and Medical School, Universitat de Girona (UdG), Girona, Spain.
authors.forename: Mònica
authors.initials: M
authors.lastname: Coll
authors.affiliation: Cardiovascular Genetics Centre, Institut d'Investigació Biomèdica de Girona (IDIBGi), Girona, Spain and Medical School, Universitat de Girona (UdG), Girona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Iglesias
authors.affiliation: Cardiovascular Genetics Centre, Institut d'Investigació Biomèdica de Girona (IDIBGi), Girona, Spain and Medical School, Universitat de Girona (UdG), Girona, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Pagans
authors.affiliation: Paediatric Arrhythmia Unit, Cardiology Department, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.
authors.forename: Georgia
authors.initials: G
authors.lastname: Sarquella-Brugada
authors.affiliation: Arrhythmia Unit, Hospital Clínic of Barcelona, University of Barcelona, Barcelona, Spain.
authors.forename: Paola
authors.initials: P
authors.lastname: Berne
authors.affiliation: Arrhythmia Unit, Hospital Clínic of Barcelona, University of Barcelona, Barcelona, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: Benito
authors.affiliation: Arrhythmia Unit, Hospital Clínic of Barcelona, University of Barcelona, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Brugada
authors.affiliation: Arrhythmia Unit, Hospital Universitario Donostia, San Sebastian, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Porres
authors.affiliation: Pediatric Cardiology Service, Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: Matilde
authors.initials: M
authors.lastname: López Zea
authors.affiliation: Arrhythmia Unit, Hospital Puerta de Hierro, Madrid, Spain.
authors.forename: Víctor
authors.initials: V
authors.lastname: Castro-Urda
authors.affiliation: Arrhythmia Unit, Hospital Puerta de Hierro, Madrid, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Fernández-Lozano
authors.affiliation: Cardiovascular Genetics Centre, Institut d'Investigació Biomèdica de Girona (IDIBGi), Girona, Spain and Medical School, Universitat de Girona (UdG), Girona, Spain; Hospital Josep Trueta, Girona, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Brugada
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D053840:Brugada Syndrome / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D015321:Gene Rearrangement / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D062548:Voltage-Gated Sodium Channel beta-2 Subunit / Q000235:genetics; D055815:Young Adult
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C117620:SCN2B protein, human; C568320:SCN5A protein, human; D062548:Voltage-Gated Sodium Channel beta-2 Subunit