Title |
Mutations in SLC12A5 in epilepsy of infancy with migrating focal seizures
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Published in |
Nature Communications, September 2015
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DOI | 10.1038/ncomms9038 |
Pubmed ID | |
Authors |
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, Henrik Stranneheim, Stephanie Tigerschiöld, Bengt Persson, Iftikhar Bangash, Krishna Das, Deborah Hughes, Nicole Lesko, Joakim Lundeberg, Rod C. Scott, Annapurna Poduri, Ingrid E. Scheffer, Holly Smith, Paul Gissen, Stephanie Schorge, Maarten E. A. Reith, Maya Topf, Dimitri M. Kullmann, Robert J. Harvey, Anna Wedell, Manju 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. |
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Geographical breakdown
Country | Count | As % |
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United States | 3 | 25% |
Japan | 1 | 8% |
United Kingdom | 1 | 8% |
Australia | 1 | 8% |
France | 1 | 8% |
Unknown | 5 | 42% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 11 | 92% |
Scientists | 1 | 8% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United Kingdom | 3 | 2% |
Finland | 2 | 1% |
Germany | 1 | <1% |
Canada | 1 | <1% |
Japan | 1 | <1% |
Unknown | 165 | 95% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 34 | 20% |
Student > Ph. D. Student | 26 | 15% |
Student > Master | 16 | 9% |
Student > Bachelor | 14 | 8% |
Other | 13 | 8% |
Other | 30 | 17% |
Unknown | 40 | 23% |
Readers by discipline | Count | As % |
---|---|---|
Neuroscience | 36 | 21% |
Agricultural and Biological Sciences | 33 | 19% |
Medicine and Dentistry | 23 | 13% |
Biochemistry, Genetics and Molecular Biology | 20 | 12% |
Pharmacology, Toxicology and Pharmaceutical Science | 5 | 3% |
Other | 8 | 5% |
Unknown | 48 | 28% |