English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/203895
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Exportar a otros formatos:

Title

Complete loss of KCNA1 activity causes neonatal epileptic encephalopathy and dyskinesia

AuthorsVerdura, Edgard; Font, Carme; Schlüter, Agatha; Ruiz, Montserrat; Fourcade, Stéphane; Casasnovas, Carlos; Castellano, Antonio; Pujol, Aurora
Issue Date2020
PublisherBMJ Publishing Group
CitationJournal of Medical Genetics 57: 132-137 (2020)
Abstract[Background] Since 1994, over 50 families affected by the episodic ataxia type 1 disease spectrum have been described with mutations in KCNA1, encoding the voltage-gated K+ channel subunit Kv1.1. All of these mutations are either transmitted in an autosomal-dominant mode or found as de novo events.
[Methods] A patient presenting with a severe combination of dyskinesia and neonatal epileptic encephalopathy was sequenced by whole-exome sequencing (WES). A candidate variant was tested using cellular assays and patch-clamp recordings.
[Results] WES revealed a homozygous variant (p.Val368Leu) in KCNA1, involving a conserved residue in the pore domain, close to the selectivity signature sequence for K+ ions (TVGYG). Functional analysis showed that mutant protein alone failed to produce functional channels in homozygous state, while coexpression with wild-type produced no effects on K+ currents, similar to wild-type protein alone. Treatment with oxcarbazepine, a sodium channel blocker, proved effective in controlling seizures.
[Conclusion] This newly identified variant is the first to be reported to act in a recessive mode of inheritance in KCNA1. These findings serve as a cautionary tale for the diagnosis of channelopathies, in which an unreported phenotypic presentation or mode of inheritance for the variant of interest can hinder the identification of causative variants and adequate treatment choice.
Publisher version (URL)http://dx.doi.org/10.1136/jmedgenet-2019-106373
URIhttp://hdl.handle.net/10261/203895
DOI10.1136/jmedgenet-2019-106373
ISSN0022-2593
E-ISSN1468-6244
Appears in Collections:(IBIS) Artículos
Files in This Item:
File Description SizeFormat 
KCNA1_activity.pdf3,78 MBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.