Mutations in SLC12A5 in epilepsy of infancy with migrating focal seizures

Nature Communications
Tommy StödbergManju A Kurian

Abstract

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.

References

Aug 7, 2002·Current Opinion in Structural Biology·Roland L Dunbrack
Sep 5, 2002·Nature Reviews. Neuroscience·Yehezkel Ben-Ari
Jun 26, 2003·Nucleic Acids Research·Narayanan EswarAndrej Sali
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Apr 9, 2005·The European Journal of Neuroscience·Janne TornbergMatti S Airaksinen
Jun 28, 2005·Nucleic Acids Research·Johannes SödingAndrei N Lupas
Sep 1, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Daria S Hekmat-ScafeMark A Tanouye
Oct 13, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Peter BlaesseHans Gerd Nothwang
Nov 1, 2006·Protein Science : a Publication of the Protein Society·Min-Yi Shen, Andrej Sali
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
Jul 18, 2009·Science·Paul L ShafferEric Gouaux
Jan 30, 2010·Bioinformatics·Aaron R Quinlan, Ira M Hall
Jun 3, 2010·The Journal of Biological Chemistry·Anna-Maria HartmannHans Gerd Nothwang
Jul 6, 2010·Nucleic Acids Research·Kai WangHakon Hakonarson
Jul 16, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Seo-Kyung ChungMark I Rees
Mar 1, 2012·Frontiers in Cellular Neuroscience·Ingrid ChammaSabine Lévi
Oct 5, 2012·American Journal of Physiology. Cell Physiology·Shane P AntrobusJohn A Payne
Feb 8, 2013·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Tetsushi SakumaTakashi Yamamoto
Sep 27, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ingrid ChammaSabine Lévi
Nov 19, 2013·Annals of Neurology·Pasquale StrianoRima Nabbout
Jun 15, 2014·EMBO Reports·Christian A Hübner

❮ Previous
Next ❯

Citations

Jan 23, 2016·Brain & Development·Ayako ItakuraYoshihiro Maegaki
Mar 18, 2016·Neuron·Nicolas DoyonYves De Koninck
Jan 8, 2016·Journal of Medical Genetics·Chiao Xin LimSarah E Heron
Apr 26, 2016·Neuropharmacology·Matthew R KelleyStephen J Moss
May 14, 2016·Developmental Medicine and Child Neurology·Carmen BarbaUNKNOWN CDG Group
Apr 6, 2017·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Knut KirmseKnut Holthoff
Nov 5, 2016·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Kristopher T KahleAnnapurna Poduri
Nov 17, 2017·Molecular Membrane Biology·Bor Luen Tang
Sep 25, 2018·Journal of Neurogenetics·Jeffrey D Calhoun, Gemma L Carvill
Nov 3, 2017·The Journal of Biological Chemistry·Leslie C ConwayTarek Z Deeb
Mar 16, 2019·Nature Communications·Vincent MagloireIvan Pavlov
Apr 30, 2019·Epilepsy Currents·Connor D Courtney, Catherine A Christian
Nov 9, 2019·Advanced Healthcare Materials·Bahareh AzimiSerena Danti
Oct 17, 2019·Annals of Neurology·Rosemary BurgessIngrid E Scheffer
May 15, 2020·Experimental Neurobiology·Ting-Wei MiZhao-Qian Teng
Apr 28, 2020·Expert Opinion on Therapeutic Targets·Phan Q DuyKristopher T Kahle
Apr 22, 2016·American Journal of Physiology. Renal Physiology·Silvana Bazúa-ValentiGerardo Gamba
Apr 18, 2020·Pflügers Archiv : European journal of physiology·Tenpei Akita, Atsuo Fukuda
Oct 12, 2019·Science·UNKNOWN International Multiple Sclerosis Genetics Consortium
Feb 6, 2020·Frontiers in Neurology·Ru LiuXiaofeng Yang
Jun 9, 2016·Human Molecular Genetics·Elizabeth E PalmerWilliam R Lagor
Sep 19, 2018·Proceedings of the National Academy of Sciences of the United States of America·Yvonne E MooreStephen J Moss
Mar 8, 2019·Frontiers in Cellular Neuroscience·Etienne CômeSabine Lévi
Dec 6, 2019·Frontiers in Cellular Neuroscience·Phan Q DuyKristopher T Kahle
Dec 24, 2019·Developmental Medicine and Child Neurology·Ingrid E SchefferHeather C Mefford
Sep 3, 2019·Neuropharmacology·Theresa AuerChristoph Schwarzer
Jan 14, 2020·European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society·Kelsey PoissonMaria Roberta Cilio

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Methods Mentioned

BETA
exome sequencing
transfection
glycosylation
genotyping
PCR
in vitro transcription
electrophoresis
dissection

Software Mentioned

Annovar
Chimera
MIP
ProSA
ConSurf
UCSC genome browser
custom scripts
SAMtools
Mosaik
Novoalign

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