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., Friis, S., Thomsen, M. B., Bundgaard, H., & 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 {\textcopyright} 2017 Elsevier B.V. All rights reserved.",
year = "2018",
month = apr,
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