A variant of KCC2 from patients with febrile seizures impairs neuronal Cl- extrusion and dendritic spine formation
AuthorPuskarjov, M; Seja, P; Heron, SE; Williams, TC; Ahmad, F; Iona, X; Oliver, KL; Grinton, BE; Vutskits, L; Scheffer, IE; ...
Source TitleEMBO Reports
University of Melbourne Author/sScheffer, Ingrid; Grinton, Bronwyn; Berkovic, Samuel; Petrou, Steven; Broderick, Karen
AffiliationFlorey Department of Neuroscience and Mental Health
Clinical School (Austin Health)
Medicine (Austin & Northern Health)
Document TypeJournal Article
CitationsPuskarjov, M., Seja, P., Heron, S. E., Williams, T. C., Ahmad, F., Iona, X., Oliver, K. L., Grinton, B. E., Vutskits, L., Scheffer, I. E., Petrou, S., Blaesse, P., Dibbens, L. M., Berkovic, S. F. & Kaila, K. (2014). A variant of KCC2 from patients with febrile seizures impairs neuronal Cl- extrusion and dendritic spine formation. EMBO REPORTS, 15 (6), pp.723-729. https://doi.org/10.1002/embr.201438749.
Access StatusOpen Access
Open Access at PMChttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197883
Genetic variation in SLC12A5 which encodes KCC2, the neuron-specific cation-chloride cotransporter that is essential for hyperpolarizing GABAergic signaling and formation of cortical dendritic spines, has not been reported in human disease. Screening of SLC12A5 revealed a co-segregating variant (KCC2-R952H) in an Australian family with febrile seizures. We show that KCC2-R952H reduces neuronal Cl(-) extrusion and has a compromised ability to induce dendritic spines in vivo and in vitro. Biochemical analyses indicate a reduced surface expression of KCC2-R952H which likely contributes to the functional deficits. Our data suggest that KCC2-R952H is a bona fide susceptibility variant for febrile seizures.
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