SCN5A mutation associated with acute myocardial infarction.
Ventricular tachycardia and fibrillation (VT/VF) complicating Brugada syndrome, a genetic disorder linked to SCN5A mutations, and VF complicating acute myocardial infarction (AMI) have both been linked to phase 2 reentry. Because of these mechanistic similarities in arrhythmogenesis, we examined the contribution of SCN5A mutations to VT/VF complicating AMI. Nineteen consecutive patients developing VF during AMI were enrolled. Wild-type (WT) and mutant SCN5A genes were co-expressed with SCN1B in TSA201 cells and studied using whole-cell patch-clamp techniques. One missense mutation (G400A) in SCN5A was detected in a conserved region among the cohort of 19 patients. A H558R polymorphism was detected on the same allele. Unlike the other 18 patients who each developed 1-2 VF episodes during acute MI, the mutation carrier developed six episodes of VT/VF within the first 12 hours. All VT/VF episodes were associated with ST segment changes and were initiated by short-coupled extrasystoles. We describe the first sodium channel mutation to be associated with the development of an arrhythmic storm during acute ischemia. These findings suggest that a loss of function in SCN5A may predispose to ischemia induced arrhythmic storm. These results could be very useful for forensic implications regarding genetic screening in relatives.
Oliva
Antonio
A
Institute of Forensic Medicine, Catholic University, School of Medicine, Largo Francesco Vito 1, Rome, Italy. antonio.oliva@rm.unicatt.it
Hu
Dan
D
Viskin
Sami
S
Carrier
Tabitha
T
Cordeiro
Jonathan M
JM
Barajas-Martinez
Hector
H
Wu
Yusheng
Y
Burashnikov
Elena
E
Brugada
Ramon
R
Rosso
Rafael
R
Guerchicoff
Alexandra
A
Pollevick
Guido
G
Pascali
Vincenzo L
VL
Antzelevitch
Charlie
C
D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D004562:Electrocardiography; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D020125:Mutation, Missense; D009203:Myocardial Infarction / Q000235:genetics*; D062554:NAV1.5 Voltage-Gated Sodium Channel; D018408:Patch-Clamp Techniques; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015222:Sodium Channels / Q000235:genetics*; D017180:Tachycardia, Ventricular / Q000235:genetics*; D014693:Ventricular Fibrillation / Q000235:genetics*
D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels