AI Article Synopsis
- - The KCC2 protein, linked to the SLC12A5 gene, is essential for regulating chloride ions in the brain, which helps control fast synaptic inhibition.
- - Researchers discovered mutations in the SLC12A5 gene that cause a severe form of epilepsy known as epilepsy of infancy with migrating focal seizures (EIMFS).
- - Problems with KCC2, such as reduced surface expression and impaired function, lead to disrupted synaptic inhibition and increased neuron activity, contributing to this early-onset epilepsy.
Article 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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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4569694 | PMC |
| http://dx.doi.org/10.1038/ncomms9038 | DOI Listing |
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