title: Ventricular tachycardia in a Brugada syndrome patient caused by a novel deletion in SCN5A.
abstract: The aim of the present study was to identify the molecular mechanism behind ventricular tachycardia in a patient with Brugada syndrome. Arrhythmias in patients with Brugada syndrome often occur during sleep. However, a 28-year-old man with no previously documented arrhythmia or syncope who experienced shortness of breath and chest pain during agitation is described. An electrocardiogram revealed monomorphic ventricular tachycardia; after he was converted to nodal rhythm, he spontaneously went into sinus rhythm, and showed classic Brugada changes with coved ST elevation in leads V(1) to V(2). Mutation analysis of SCN5A revealed a novel mutation, 3480 deletion T frame shift mutation, resulting in premature truncation of the protein. Heterologous expression of this truncated protein in human embryonic kidney 293 cells showed a markedly reduced protein expression level. By performing whole-cell patch clamp experiments using human embryonic kidney 293 cells transfected with the mutated SCN5A, no current could be recorded. Hence, the results suggest that the patient suffered from haploinsufficiency of Na(v)1.5, and that this mutation was the cause of his Brugada syndrome.
authors.affiliation: Department of Cardiology, Copenhagen University Hospital, Blegdamsvej, Denmark. tfelt@dadlnet.dk
authors.forename: J
authors.initials: J
authors.lastname: Tfelt-Hansen
authors.forename: T
authors.initials: T
authors.lastname: Jespersen
authors.forename: J
authors.initials: J
authors.lastname: Hofman-Bang
authors.forename: H Borger
authors.initials: HB
authors.lastname: Rasmussen
authors.forename: P
authors.initials: P
authors.lastname: Cedergreen
authors.forename: F
authors.initials: F
authors.lastname: Skovby
authors.forename: H
authors.initials: H
authors.lastname: Abriel
authors.forename: J Hastrup
authors.initials: JH
authors.lastname: Svendsen
authors.forename: Soren-Peter
authors.initials: SP
authors.lastname: Olesen
authors.forename: M
authors.initials: M
authors.lastname: Christiansen
authors.forename: S
authors.initials: S
authors.lastname: Haunso
mesh_terms: D000328:Adult; D053840:Brugada Syndrome / Q000235:genetics*; D002872:Chromosome Deletion; D004562:Electrocardiography; D016368:Frameshift Mutation; D006801:Humans; D008297:Male; D009124:Muscle Proteins / Q000235:genetics*; D062554:NAV1.5 Voltage-Gated Sodium Channel; D018408:Patch-Clamp Techniques; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D015222:Sodium Channels / Q000235:genetics*; D017180:Tachycardia, Ventricular / Q000235:genetics*; D014162:Transfection
chemical_list: D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels