title: SCN1B gene variants in Brugada Syndrome: a study of 145 SCN5A-negative patients.
abstract: Brugada syndrome is characterised by a typical ECG with ST segment elevation in the right precordial leads. Individuals with this condition are susceptible to ventricular arrhythmias and sudden cardiac death. The principal gene responsible for this syndrome is SCN5A, which encodes the α-subunit of the Nav1.5 voltage-gated sodium channel. Mutations involving other genes have been increasingly reported, but their contribution to Brugada syndrome has been poorly investigated. Here we focused on the SCN1B gene, which encodes the β1-subunit of the voltage-gated sodium channel and its soluble β1b isoform. SCN1B mutations have been associated with Brugada syndrome as well as with other cardiac arrhythmias and familial epilepsy. In this study, we have analysed SCN1B exons (including the alternatively-spliced exon 3A) and 3'UTR in 145 unrelated SCN5A-negative patients from a single centre. We took special care to report all identified variants (including polymorphisms), following the current nomenclature guidelines and considering both isoforms. We found two known and two novel (and likely deleterious) SCN1B variants. We also found two novel changes with low evidence of pathogenicity. Our findings contribute more evidence regarding the occurrence of SCN1B variants in Brugada syndrome, albeit with a low prevalence, which is in agreement with previous reports.
authors.affiliation: 1] Medical Genetics, University of Torino, Dept. Clinical &Biological Sciences, Torino, Italy [2] Medical Genetics, San Luigi University Hospital, Orbassano, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Ricci
authors.affiliation: Medical Genetics, University of Torino, Dept. Clinical &Biological Sciences, Torino, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Menegon
authors.affiliation: Medical Genetics, University of Torino, Dept. Clinical &Biological Sciences, Torino, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Vatrano
authors.affiliation: 1] Medical Genetics, University of Torino, Dept. Clinical &Biological Sciences, Torino, Italy [2] Medical Genetics, San Luigi University Hospital, Orbassano, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Mandrile
authors.affiliation: 1] Division of Cardiology, Città della Salute e della Scienza Hospital, Torino, Italy [2] Division of Cardiology, University of Torino, Dept. Medical Sciences, Torino, Italy.
authors.forename: Natascia
authors.initials: N
authors.lastname: Cerrato
authors.affiliation: Cardiology Unit, San Luigi University Hospital, Orbassano, Italy.
authors.forename: Paula
authors.initials: P
authors.lastname: Carvalho
authors.affiliation: 1] Medical Genetics, University of Torino, Dept. Clinical &Biological Sciences, Torino, Italy [2] Medical Genetics, San Luigi University Hospital, Orbassano, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: De Marchi
authors.affiliation: 1] Division of Cardiology, Città della Salute e della Scienza Hospital, Torino, Italy [2] Division of Cardiology, University of Torino, Dept. Medical Sciences, Torino, Italy.
authors.forename: Fiorenzo
authors.initials: F
authors.lastname: Gaita
authors.affiliation: 1] Division of Cardiology, Città della Salute e della Scienza Hospital, Torino, Italy [2] Division of Cardiology, University of Torino, Dept. Medical Sciences, Torino, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Giustetto
authors.affiliation: 1] Medical Genetics, University of Torino, Dept. Clinical &Biological Sciences, Torino, Italy [2] Medical Genetics, San Luigi University Hospital, Orbassano, Italy.
authors.forename: Daniela Francesca
authors.initials: DF
authors.lastname: Giachino
mesh_terms: D020413:3' Untranslated Regions; D000293:Adolescent; D000328:Adult; D000368:Aged; D053840:Brugada Syndrome / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D002648:Child; D016757:Death, Sudden, Cardiac / Q000209:etiology / Q000473:pathology; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics*; D011110:Polymorphism, Genetic; D062547:Voltage-Gated Sodium Channel beta-1 Subunit / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D062554:NAV1.5 Voltage-Gated Sodium Channel; C470379:SCN1B protein, human; D062547:Voltage-Gated Sodium Channel beta-1 Subunit