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Journal articles
Characterization of novel KCNH2 mutations in type 2 long QT syndrome manifesting as seizures.: Characterizing novel KCNH2 mutations
Abstract : BACKGROUND: Long QT syndrome (LQTS) is characterized by corrected QT interval prolongation leading to torsades de pointes and sudden cardiac death. LQTS type 2 (LQTS2) is caused by mutations in the KCNH2 gene, leading to a reduction of the rapidly activating delayed rectifier K+ current and loss of human ether-à-go-go-related gene (hERG) channel function by different mechanisms. Triggers for life-threatening arrhythmias in LQTS2 are often auditory stimuli. OBJECTIVES: To screen KCNH2 for mutations in patients with LQTS2 on an electrocardiogram and auditory-induced syncope interpreted as seizures and sudden cardiac death, and to analyze their impact on the channel function in vitro. METHODS: The KCNH2 gene was screened for mutations in the index patients of three families. The novel mutations were reproduced in vitro using site-directed mutagenesis and characterized using the Xenopus oocyte expression system in voltage clamp mode. RESULTS: Novel KCNH2 mutations (Y493F, A429P and del234-241) were identified in the index patients with mostly typical LQTS2 features on their electrocardiograms. The biochemical data revealed a trafficking defect. The biophysical data revealed a loss of function when mutated hERG channels were coexpressed with the wild type. CONCLUSIONS: In all families, at least one patient carrying the mutation had a history of seizures after auditory stimuli, which is a major trigger for arrhythmic events in LQTS2. Seizures are likely due to cardiac syncope as a consequence of mutation-induced loss of function of the rapidly activating delayed rectifier K+ current.
Cited literature [5 references]
https://www.hal.inserm.fr/inserm-00409709
Contributor : Georges Christé <>
Submitted on : Wednesday, May 21, 2014 - 9:12:00 AM
Last modification on : Monday, July 20, 2020 - 1:06:03 PM
Long-term archiving on: : Thursday, August 21, 2014 - 10:35:36 AM
Contributor : Georges Christé <>
Submitted on : Wednesday, May 21, 2014 - 9:12:00 AM
Last modification on : Monday, July 20, 2020 - 1:06:03 PM
Long-term archiving on: : Thursday, August 21, 2014 - 10:35:36 AM
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