A rare loss-of-function SCN5A variant is associated with lidocaine-induced ventricular fibrillation.
The human genome contains over 4 million variant sites, as compared with the reference genome, including rare sequence variants, which have the potential to exert large phenotypic effects, such as susceptibility to drug toxicity. We report identification and functional characterization of a rare non-synonymous (p.A1427S) variant in the SCN5A gene that was associated with incessant and lethal ventricular tachycardia and fibrillation after administration of lidocaine to a patient with acute myocardial infarction. The variant, located in a highly conserved domain distinct from the predicted lidocaine-binding site, decreased peak current density of the sodium channel. With the increasing availability of the whole exome and whole genome sequencing data, it would be possible to identify and characterize rare variants in SCN5A that might predispose to lethal ventricular arrhythmias.
Cardiovascular Department, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Q
Q
Xiong
Cardiovascular Department, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
L
L
Cao
Cardiovascular Department, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
J
J
Hu
1] Center for Cardiovascular Genetics at The University of Texas Health Science Center-Houston and, Houston, TX, USA [2] Texas Heart Institute, Houston, TX, USA.
A J
AJ
Marian
1] Cardiovascular Department, The Second Affiliated Hospital of Nanchang University, Nanchang, China [2] The Key Laboratory of Molecular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
K
K
Hong
D000779:Anesthetics, Local / Q000009:adverse effects*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008012:Lidocaine / Q000009:adverse effects*; D008875:Middle Aged; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics*; D014693:Ventricular Fibrillation / Q000139:chemically induced*
D000779:Anesthetics, Local; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D008012:Lidocaine