IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms9038.html
   My bibliography  Save this article

Mutations in SLC12A5 in epilepsy of infancy with migrating focal seizures

Author

Listed:
  • Tommy Stödberg

    (Karolinska Institutet
    Neuropediatric Unit, Karolinska University Hospital)

  • Amy McTague

    (Molecular Neurosciences, Developmental Neurosciences Programme, UCL Institute of Child Health
    Great Ormond Street Hospital)

  • Arnaud J. Ruiz

    (UCL School of Pharmacy)

  • Hiromi Hirata

    (Graduate School of Science and Engineering, Aoyama Gakuin University
    Center for Frontier Research, National Institute of Genetics
    PREST, Japan Science and Technology Agency)

  • Juan Zhen

    (New York University School of Medicine)

  • Philip Long

    (UCL School of Pharmacy)

  • Irene Farabella

    (Institute of Structural and Molecular Biology, Birkbeck College, University of London)

  • Esther Meyer

    (Molecular Neurosciences, Developmental Neurosciences Programme, UCL Institute of Child Health)

  • Atsuo Kawahara

    (Laboratory for Developmental Biology, Graduate School of Medical Science, University of Yamanashi)

  • Grace Vassallo

    (Royal Manchester Children’s Hospital)

  • Stavros M. Stivaros

    (Royal Manchester Children’s Hospital
    Imaging Science, School of Population Health, University of Manchester)

  • Magnus K. Bjursell

    (Science for Life Laboratory, Center for Molecular Medicine, Karolinska Institutet
    Present address: AstraZeneca R&D Mölndal, 431 83 Mölndal, Sweden.)

  • Henrik Stranneheim

    (Science for Life Laboratory, Center for Molecular Medicine, Karolinska Institutet
    Centre for Inherited Metabolic Diseases, Karolinska University Hospital)

  • Stephanie Tigerschiöld

    (Science for Life Laboratory, Center for Molecular Medicine, Karolinska Institutet
    Centre for Inherited Metabolic Diseases, Karolinska University Hospital)

  • Bengt Persson

    (Science for Life Laboratory, Uppsala University
    Science for Life Laboratory, Karolinska Institutet)

  • Iftikhar Bangash

    (Royal Oldham Hospital)

  • Krishna Das

    (Great Ormond Street Hospital
    Young Epilepsy)

  • Deborah Hughes

    (UCL Institute of Neurology)

  • Nicole Lesko

    (Centre for Inherited Metabolic Diseases, Karolinska University Hospital
    Karolinska Institutet)

  • Joakim Lundeberg

    (Science for Life Laboratory, School of Biotechnology, Royal Institute of Technology)

  • Rod C. Scott

    (Great Ormond Street Hospital
    University of Vermont College of Medicine
    Fletcher Allen Health Care
    Clinical Neurosciences, Developmental Neurosciences Programme, UCL Institute of Child Health)

  • Annapurna Poduri

    (Epilepsy Genetics Programme, Boston Children’s Hospital
    Harvard Medical School)

  • Ingrid E. Scheffer

    (University of Melbourne, Austin Health and Royal Children’s Hospital
    Florey Institute)

  • Holly Smith

    (MRC Laboratory for Molecular Cell Biology, UCL)

  • Paul Gissen

    (MRC Laboratory for Molecular Cell Biology, UCL
    Great Ormond Street Hospital
    Genetics and Genomic Medicine, Institute of Child Health, UCL)

  • Stephanie Schorge

    (UCL Institute of Neurology)

  • Maarten E. A. Reith

    (New York University School of Medicine
    New York University School of Medicine)

  • Maya Topf

    (Institute of Structural and Molecular Biology, Birkbeck College, University of London)

  • Dimitri M. Kullmann

    (UCL Institute of Neurology)

  • Robert J. Harvey

    (UCL School of Pharmacy)

  • Anna Wedell

    (Science for Life Laboratory, Center for Molecular Medicine, Karolinska Institutet
    Centre for Inherited Metabolic Diseases, Karolinska University Hospital)

  • Manju A. Kurian

    (Molecular Neurosciences, Developmental Neurosciences Programme, UCL Institute of Child Health
    Great Ormond Street Hospital)

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.

Suggested Citation

  • Tommy Stödberg & Amy McTague & Arnaud J. Ruiz & Hiromi Hirata & Juan Zhen & Philip Long & Irene Farabella & Esther Meyer & Atsuo Kawahara & Grace Vassallo & Stavros M. Stivaros & Magnus K. Bjursell & , 2015. "Mutations in SLC12A5 in epilepsy of infancy with migrating focal seizures," Nature Communications, Nature, vol. 6(1), pages 1-9, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9038
    DOI: 10.1038/ncomms9038
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms9038
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms9038?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9038. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.