TY  - JOUR
A1  - Scheiper-Welling, Stefanie
A1  - Zuccolini, Paolo
A1  - Rauh, Oliver
A1  - Beckmann, Britt-Maria
A1  - Geisen, Christof
A1  - Moroni, Anna
A1  - Thiel, Gerhard
A1  - Kauferstein, Silke
T1  - Characterization of an N-terminal Nav1.5 channel variant – a potential risk factor for arrhythmias and sudden death?
T2  - BMC Medical Genetics
N2  - Background: Alterations in the SCN5A gene encoding the cardiac sodium channel Nav1.5 have been linked to a number of arrhythmia syndromes and diseases including long-QT syndrome (LQTS), Brugada syndrome (BrS) and dilative cardiomyopathy (DCM), which may predispose to fatal arrhythmias and sudden death. We identified the heterozygous variant c.316A > G, p.(Ser106Gly) in a 35-year-old patient with survived cardiac arrest. In the present study, we aimed to investigate the functional impact of the variant to clarify the medical relevance.
Methods: Mutant as well as wild type GFP tagged Nav1.5 channels were expressed in HEK293 cells. We performed functional characterization experiments using patch-clamp technique.
Results: Electrophysiological measurements indicated, that the detected missense variant alters Nav1.5 channel functionality leading to a gain-of-function effect. Cells expressing S106G channels show an increase in Nav1.5 current over the entire voltage window.
Conclusion: The results support the assumption that the detected sequence aberration alters Nav1.5 channel function and may predispose to cardiac arrhythmias and sudden cardiac death.
KW  - Arrhythmia syndromes
KW  - Sudden death
KW  - Cardiac arrest
KW  - SCN5A
KW  - Functional characterization
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/80736
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-807366
SN  - 1471-2350
N1  - The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
N1  - The peer review history for this article is available at: https://bmcmedgenet.biomedcentral.com/articles/10.1186/s12881-020-01170-3/peer-review.
N1  - Open Access funding enabled and organized by Projekt DEAL.
VL  - 21
IS  - 1, art. 227
SP  - 1
EP  - 9
PB  - BioMed Central ; Springer
CY  - London ; Berlin ; Heidelberg
ER  -