Multifocal atrial and ventricular premature contractions with an increased risk of dilated cardiomyopathy caused by a Nav1.5 gain-of-function mutation (G213D)

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Multifocal atrial and ventricular premature contractions with an increased risk of dilated cardiomyopathy caused by a Nav1.5 gain-of-function mutation (G213D). / Calloe, Kirstine; Broendberg, Anders K; Christensen, Alex H; Pedersen, Lisbeth N; Olesen, Morten S; de Los Angeles Tejada, Maria; Friis, Soren; Thomsen, Morten B; Bundgaard, Henning; Jensen, Henrik K.

I: International Journal of Cardiology, Bind 257, 15.04.2018, s. 160-167.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Calloe, K, Broendberg, AK, Christensen, AH, Pedersen, LN, Olesen, MS, de Los Angeles Tejada, M, Friis, S, Thomsen, MB, Bundgaard, H & Jensen, HK 2018, 'Multifocal atrial and ventricular premature contractions with an increased risk of dilated cardiomyopathy caused by a Nav1.5 gain-of-function mutation (G213D)', International Journal of Cardiology, bind 257, s. 160-167. https://doi.org/10.1016/j.ijcard.2017.11.095

APA

Calloe, K., Broendberg, A. K., Christensen, A. H., Pedersen, L. N., Olesen, M. S., de Los Angeles Tejada, M., ... Jensen, H. K. (2018). Multifocal atrial and ventricular premature contractions with an increased risk of dilated cardiomyopathy caused by a Nav1.5 gain-of-function mutation (G213D). International Journal of Cardiology, 257, 160-167. https://doi.org/10.1016/j.ijcard.2017.11.095

Vancouver

Calloe K, Broendberg AK, Christensen AH, Pedersen LN, Olesen MS, de Los Angeles Tejada M o.a. Multifocal atrial and ventricular premature contractions with an increased risk of dilated cardiomyopathy caused by a Nav1.5 gain-of-function mutation (G213D). International Journal of Cardiology. 2018 apr 15;257:160-167. https://doi.org/10.1016/j.ijcard.2017.11.095

Author

Calloe, Kirstine ; Broendberg, Anders K ; Christensen, Alex H ; Pedersen, Lisbeth N ; Olesen, Morten S ; de Los Angeles Tejada, Maria ; Friis, Soren ; Thomsen, Morten B ; Bundgaard, Henning ; Jensen, Henrik K. / Multifocal atrial and ventricular premature contractions with an increased risk of dilated cardiomyopathy caused by a Nav1.5 gain-of-function mutation (G213D). I: International Journal of Cardiology. 2018 ; Bind 257. s. 160-167.

Bibtex

@article{51b148c5f99c4d03a55838385ab106e8,
title = "Multifocal atrial and ventricular premature contractions with an increased risk of dilated cardiomyopathy caused by a Nav1.5 gain-of-function mutation (G213D)",
abstract = "BACKGROUND: SCN5A mutations can lead to different cardiac diseases. Recently, SCN5A mutations have been linked to the clinical entity multifocal ectopic Purkinje-related premature contractions (MEPPC) characterized by ventricular ectopy and dilated cardiomyopathy.METHODS & RESULTS: A family with a uniform MEPPC-like phenotype, associated with complex atrial and ventricular arrhythmias and dilated cardiomyopathy caused by a high frequency of ventricular ectopy was clinically assessed. Screening of the SCN5A gene revealed a missense mutation in the linker between segments 3 and 4 in domain 1 of the Nav1.5 protein, resulting in a glycine to aspartate substitution at position 213 (G213D). The phenotype co-segregated with the missense mutation. Electrophysiological studies of wild type (WT) hNav1.5 and hNav1.5_G213D expressed in CHO-K cells showed that the voltage of half-maximal activation (V½) was significantly more negative for hNav1.5_G213D compared to WT (V½=-38.7±0.5mV for WT and V½=-42.4±0.5mV for G213D; P<0.001). This suggests activation of Nav1.5_G231D at more negative potentials. The V½of steady-state inactivation was significantly shifted towards more positive values for Nav1.5_G213D (V½=-86.7±0.2mV for WT and -82.2±0.3mV for G213D; P<0.001), also contributing to a gain-of-function phenotype. Flecainide and amiodarone markedly reduced premature atrial and ventricular contractions in four patients.CONCLUSION: The Nav1.5_G213D mutation is associated with a gain-of-function phenotype, multifocal atrial and ventricular ectopy and dilated cardiomyopathy. Since patients with a MEPPC-like phenotype may specifically benefit from Class-1 antiarrhythmic drugs or amiodarone, clinical identification of this disease entity is important.",
author = "Kirstine Calloe and Broendberg, {Anders K} and Christensen, {Alex H} and Pedersen, {Lisbeth N} and Olesen, {Morten S} and {de Los Angeles Tejada}, Maria and Soren Friis and Thomsen, {Morten B} and Henning Bundgaard and Jensen, {Henrik K}",
note = "Copyright {\circledC} 2017 Elsevier B.V. All rights reserved.",
year = "2018",
month = "4",
day = "15",
doi = "10.1016/j.ijcard.2017.11.095",
language = "English",
volume = "257",
pages = "160--167",
journal = "International Journal of Cardiology",
issn = "0167-5273",
publisher = "Elsevier Ireland Ltd",

}

RIS

TY - JOUR

T1 - Multifocal atrial and ventricular premature contractions with an increased risk of dilated cardiomyopathy caused by a Nav1.5 gain-of-function mutation (G213D)

AU - Calloe, Kirstine

AU - Broendberg, Anders K

AU - Christensen, Alex H

AU - Pedersen, Lisbeth N

AU - Olesen, Morten S

AU - de Los Angeles Tejada, Maria

AU - Friis, Soren

AU - Thomsen, Morten B

AU - Bundgaard, Henning

AU - Jensen, Henrik K

N1 - Copyright © 2017 Elsevier B.V. All rights reserved.

PY - 2018/4/15

Y1 - 2018/4/15

N2 - BACKGROUND: SCN5A mutations can lead to different cardiac diseases. Recently, SCN5A mutations have been linked to the clinical entity multifocal ectopic Purkinje-related premature contractions (MEPPC) characterized by ventricular ectopy and dilated cardiomyopathy.METHODS & RESULTS: A family with a uniform MEPPC-like phenotype, associated with complex atrial and ventricular arrhythmias and dilated cardiomyopathy caused by a high frequency of ventricular ectopy was clinically assessed. Screening of the SCN5A gene revealed a missense mutation in the linker between segments 3 and 4 in domain 1 of the Nav1.5 protein, resulting in a glycine to aspartate substitution at position 213 (G213D). The phenotype co-segregated with the missense mutation. Electrophysiological studies of wild type (WT) hNav1.5 and hNav1.5_G213D expressed in CHO-K cells showed that the voltage of half-maximal activation (V½) was significantly more negative for hNav1.5_G213D compared to WT (V½=-38.7±0.5mV for WT and V½=-42.4±0.5mV for G213D; P<0.001). This suggests activation of Nav1.5_G231D at more negative potentials. The V½of steady-state inactivation was significantly shifted towards more positive values for Nav1.5_G213D (V½=-86.7±0.2mV for WT and -82.2±0.3mV for G213D; P<0.001), also contributing to a gain-of-function phenotype. Flecainide and amiodarone markedly reduced premature atrial and ventricular contractions in four patients.CONCLUSION: The Nav1.5_G213D mutation is associated with a gain-of-function phenotype, multifocal atrial and ventricular ectopy and dilated cardiomyopathy. Since patients with a MEPPC-like phenotype may specifically benefit from Class-1 antiarrhythmic drugs or amiodarone, clinical identification of this disease entity is important.

AB - BACKGROUND: SCN5A mutations can lead to different cardiac diseases. Recently, SCN5A mutations have been linked to the clinical entity multifocal ectopic Purkinje-related premature contractions (MEPPC) characterized by ventricular ectopy and dilated cardiomyopathy.METHODS & RESULTS: A family with a uniform MEPPC-like phenotype, associated with complex atrial and ventricular arrhythmias and dilated cardiomyopathy caused by a high frequency of ventricular ectopy was clinically assessed. Screening of the SCN5A gene revealed a missense mutation in the linker between segments 3 and 4 in domain 1 of the Nav1.5 protein, resulting in a glycine to aspartate substitution at position 213 (G213D). The phenotype co-segregated with the missense mutation. Electrophysiological studies of wild type (WT) hNav1.5 and hNav1.5_G213D expressed in CHO-K cells showed that the voltage of half-maximal activation (V½) was significantly more negative for hNav1.5_G213D compared to WT (V½=-38.7±0.5mV for WT and V½=-42.4±0.5mV for G213D; P<0.001). This suggests activation of Nav1.5_G231D at more negative potentials. The V½of steady-state inactivation was significantly shifted towards more positive values for Nav1.5_G213D (V½=-86.7±0.2mV for WT and -82.2±0.3mV for G213D; P<0.001), also contributing to a gain-of-function phenotype. Flecainide and amiodarone markedly reduced premature atrial and ventricular contractions in four patients.CONCLUSION: The Nav1.5_G213D mutation is associated with a gain-of-function phenotype, multifocal atrial and ventricular ectopy and dilated cardiomyopathy. Since patients with a MEPPC-like phenotype may specifically benefit from Class-1 antiarrhythmic drugs or amiodarone, clinical identification of this disease entity is important.

U2 - 10.1016/j.ijcard.2017.11.095

DO - 10.1016/j.ijcard.2017.11.095

M3 - Journal article

C2 - 29506689

VL - 257

SP - 160

EP - 167

JO - International Journal of Cardiology

JF - International Journal of Cardiology

SN - 0167-5273

ER -

ID: 192383970