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Citations to this article

The E1784K mutation in SCN5A is associated with mixed clinical phenotype of type 3 long QT syndrome
Naomasa Makita, … , Alfred L. George Jr., Dan M. Roden
Naomasa Makita, … , Alfred L. George Jr., Dan M. Roden
Published May 1, 2008
Citation Information: J Clin Invest. 2008;118(6):2219-2229. https://doi.org/10.1172/JCI34057.
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Research Article Cardiology Article has an altmetric score of 3

The E1784K mutation in SCN5A is associated with mixed clinical phenotype of type 3 long QT syndrome

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Abstract

Phenotypic overlap of type 3 long QT syndrome (LQT3) with Brugada syndrome (BrS) is observed in some carriers of mutations in the Na channel SCN5A. While this overlap is important for patient management, the clinical features, prevalence, and mechanisms underlying such overlap have not been fully elucidated. To investigate the basis for this overlap, we genotyped a cohort of 44 LQT3 families of multiple ethnicities from 7 referral centers and found a high prevalence of the E1784K mutation in SCN5A. Of 41 E1784K carriers, 93% had LQT3, 22% had BrS, and 39% had sinus node dysfunction. Heterologously expressed E1784K channels showed a 15.0-mV negative shift in the voltage dependence of Na channel inactivation and a 7.5-fold increase in flecainide affinity for resting-state channels, properties also seen with other LQT3 mutations associated with a mixed clinical phenotype. Furthermore, these properties were absent in Na channels harboring the T1304M mutation, which is associated with LQT3 without a mixed clinical phenotype. These results suggest that a negative shift of steady-state Na channel inactivation and enhanced tonic block by class IC drugs represent common biophysical mechanisms underlying the phenotypic overlap of LQT3 and BrS and further indicate that class IC drugs should be avoided in patients with Na channels displaying these behaviors.

Authors

Naomasa Makita, Elijah Behr, Wataru Shimizu, Minoru Horie, Akihiko Sunami, Lia Crotti, Eric Schulze-Bahr, Shigetomo Fukuhara, Naoki Mochizuki, Takeru Makiyama, Hideki Itoh, Michael Christiansen, Pascal McKeown, Koji Miyamoto, Shiro Kamakura, Hiroyuki Tsutsui, Peter J. Schwartz, Alfred L. George Jr., Dan M. Roden

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2010 2009 Total
Citations: 2 4 4 5 8 7 4 5 5 9 6 8 9 3 3 2 84
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Citations to this article in year 2010 (3)

Title and authors Publication Year
Dual Variation in  SCN5A  and  CACNB2b  Underlies the Development of Cardiac Conduction Disease without Brugada Syndrome
D Hu, H Barajas-Martinez, VV Nesterenko, R Pfeiffer, A Guerchicoff, JM Cordeiro, AB Curtis, GD Pollevick, Y Wu, E Burashnikov, C Antzelevitch
Pacing and clinical electrophysiology : PACE 2010
Congenital insensitivity to pain: novel SCN9A missense and in-frame deletion mutations
JJ Cox, J Sheynin, Z Shorer, F Reimann, AK Nicholas, L Zubovic, M Baralle, E Wraige, E Manor, J Levy, CG Woods, R Parvari
Human Mutation 2010
R231C mutation in KCNQ1 causes long QT syndrome type 1 and familial atrial fibrillation
DC Bartos, S Duchatelet, DE Burgess, D Klug, I Denjoy, R Peat, JM Lupoglazoff, V Fressart, M Berthet, MJ Ackerman, CT January, P Guicheney, BP Delisle
Heart rhythm : the official journal of the Heart Rhythm Society 2010

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