Mutations in SLC12A5 in epilepsy of infancy with migrating focal seizures
2015 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 6, 8038Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2015. Vol. 6, 8038
Pediatrics Cell and Molecular Biology
IdentifiersURN: urn:nbn:se:uu:diva-267073DOI: 10.1038/ncomms9038ISI: 000362945300001PubMedID: 26333769OAI: oai:DiVA.org:uu-267073DiVA: diva2:872961
FunderEU, European Research CouncilSwedish Research Council, 12198Wellcome trustStockholm County CouncilKnut and Alice Wallenberg FoundationNIH (National Institute of Health)