Mutations in SLC12A5 in epilepsy of infancy with migrating focal seizures

T Stödberg; A McTague; A J Ruiz; H Hirata; J Zhen; P Long; I Farabella; E Meyer; A Kawahara; G Vassallo; S M Stivaros; M K Bjursell; H Stranneheim; S Tigerschiöld; B Persson; I Bangash; K Das; D Hughes; N Lesko; J Lundeberg; R C Scott; A Poduri; I E Scheffer; H Smith; P Gissen; S Schorge; M E A Reith; M Topf; D M Kullmann; Robert J Harvey; A Wedell; M A Kurian

doi:10.1038/ncomms9038

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Mutations in SLC12A5 in epilepsy of infancy with migrating focal seizures

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Mutations in SLC12A5 in epilepsy of infancy with migrating focal seizures

T Stödberg, A McTague, A J Ruiz, H Hirata, J Zhen, P Long, I Farabella, E Meyer, A Kawahara, G Vassallo, …

Nature Communications, Vol.6, pp.1-9

2015

DOI: https://doi.org/10.1038/ncomms9038

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Abstract

disease genetics

epilepsy

glycosylation

mutation

The potassium-chloride co-transporter KCC2, encoded by SLC12A5, plays a fundamental role in fast synaptic inhibition by maintaining a hyperpolarizing gradient for chloride ions. KCC2 dysfunction has been implicated in human epilepsy, but to date, no monogenic KCC2-related epilepsy disorders have been described. Here we show recessive loss-of-function SLC12A5 mutations in patients with a severe infantile-onset pharmacoresistant epilepsy syndrome, epilepsy of infancy with migrating focal seizures (EIMFS). Decreased KCC2 surface expression, reduced protein glycosylation and impaired chloride extrusion contribute to loss of KCC2 activity, thereby impairing normal synaptic inhibition and promoting neuronal excitability in this early-onset epileptic encephalopathy. © 2015 Macmillan Publishers Limited.

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Title: Mutations in SLC12A5 in epilepsy of infancy with migrating focal seizures
Authors: T Stödberg (Author) - Karolinska Institutet
A McTague (Author) - University College London
A J Ruiz (Author) - University College London
H Hirata (Author) - Aoyama Gakuin University
J Zhen (Author) - New York University School of Medicine
P Long (Author) - University College London
I Farabella (Author) - Birkbeck, University of London
E Meyer (Author) - University College London
A Kawahara (Author) - University of Yamanashi
G Vassallo (Author) - Royal Manchester Children's Hospital
S M Stivaros (Author) - Royal Manchester Children's Hospital
M K Bjursell (Author) - Karolinska Institutet
H Stranneheim (Author) - Karolinska Institutet
S Tigerschiöld (Author) - Karolinska University Hospital
B Persson (Author) - Uppsala University
I Bangash (Author) - Royal Oldham Hospital
K Das (Author) - Great Ormond Street Hospital
D Hughes (Author) - University College London
N Lesko (Author) - Karolinska University Hospital
J Lundeberg (Author) - KTH Royal Institute of Technology
R C Scott (Author) - Great Ormond Street Hospital
A Poduri (Author) - Boston Children's Hospital, United States
I E Scheffer (Author) - The University of Melbourne
H Smith (Author) - University College London
P Gissen (Author) - University College London
S Schorge (Author) - University College London
M E A Reith (Author) - New York University School of Medicine
M Topf (Author) - Birkbeck, University of London
D M Kullmann (Author) - University College London
Robert J Harvey (Author) - University College London
A Wedell (Author) - Karolinska Institutet
M A Kurian (Author) - University College London
Publication details: Nature Communications, Vol.6, pp.1-9
Publisher: Nature Publishing Group
Date published: 2015
DOI: 10.1038/ncomms9038
ISSN: 2041-1723; 2041-1723
Copyright note: Copyright © 2015 The Authors. This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. You are not required to obtain permission to reuse this article. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Organisation Unit: School of Health; School of Health and Sport Sciences - Legacy; Thompson Institute; Centre for Bioinnovation; School of Health and Behavioural Sciences - Legacy
Language: English
Record Identifier: 99450536602621
Output Type: Journal article

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Web Of Science research areas: Neurosciences

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