BackgroundAlterations in the SCN5A gene encoding the cardiac sodium channel Na(v)1.5 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.MethodsMutant as well as wild type GFP tagged Na(v)1.5 channels were expressed in HEK293 cells. We performed functional characterization experiments using patch-clamp technique.ResultsElectrophysiological 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 Na(v)1.5 current over the entire voltage window.ConclusionThe results support the assumption that the detected sequence aberration alters Na(v)1.5 channel function and may predispose to cardiac arrhythmias and sudden cardiac death.

Characterization of an N-terminal Nav1.5 channel variant - a potential risk factor for arrhythmias and sudden death? / S. Scheiper-Welling, P. Zuccolini, O. Rauh, B. Beckmann, C. Geisen, A. Moroni, G. Thiel, S. Kauferstein. - In: BMC MEDICAL GENETICS. - ISSN 1471-2350. - 21:1(2020), pp. 227.1-227.9. [10.1186/s12881-020-01170-3]

Characterization of an N-terminal Nav1.5 channel variant - a potential risk factor for arrhythmias and sudden death?

P. Zuccolini;A. Moroni;
2020

Abstract

BackgroundAlterations in the SCN5A gene encoding the cardiac sodium channel Na(v)1.5 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.MethodsMutant as well as wild type GFP tagged Na(v)1.5 channels were expressed in HEK293 cells. We performed functional characterization experiments using patch-clamp technique.ResultsElectrophysiological 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 Na(v)1.5 current over the entire voltage window.ConclusionThe results support the assumption that the detected sequence aberration alters Na(v)1.5 channel function and may predispose to cardiac arrhythmias and sudden cardiac death.
Arrhythmia syndromes; Cardiac arrest; Functional characterization; SCN5A; Sudden death;
Settore BIO/09 - Fisiologia
2020
19-nov-2020
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/1049609
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