TY - JOUR
T1 - Ventricular tachycardia in a Brugada syndrome patient caused by a novel deletion in SCN5A
AU - Tfelt-Hansen, J
AU - Jespersen, T
AU - Hofman-Bang, J
AU - Rasmussen, H Borger
AU - Cedergreen, P
AU - Skovby, F
AU - Abriel, H
AU - Svendsen, J Hastrup
AU - Olesen, Soren-Peter
AU - Christiansen, M
AU - Haunso, S
N1 - Keywords: Adult; Brugada Syndrome; Chromosome Deletion; Electrocardiography; Frameshift Mutation; Humans; Male; Muscle Proteins; Patch-Clamp Techniques; Pedigree; Polymorphism, Single-Stranded Conformational; Sodium Channels; Tachycardia, Ventricular; Transfection
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
M3 - Journal article
C2 - 19279983
SN - 0828-282X
VL - 25
SP - 156
EP - 160
JO - Canadian Journal of Cardiology
JF - Canadian Journal of Cardiology
IS - 3
ER -