Puskarjov M Seja P Heron SE Williams TC Ahmad F Iona X Oliver KL Grinton BE Vutskits L Scheffer IE Petrou S Blaesse P Dibbens LM Berkovic SF Kaila K 2014 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. https://sonar.ch/global/documents/171011 eng info:eu-repo/semantics/altIdentifier/doi/10.1002/embr.201438749 info:eu-repo/semantics/altIdentifier/pmid/24668262 EMBO reports. - 2014 KCC2 dendritic spines febrile seizures genic intolerance mutation Amino Acid Sequence Animals Australia Blotting, Western Chlorides Dendritic Spines Genetic Predisposition to Disease Humans Mice Mice, Inbred ICR Microscopy, Fluorescence Models, Molecular Molecular Sequence Data Mutation, Missense Neurons Pedigree Protein Conformation Rats Rats, Wistar Seizures, Febrile Statistics, Nonparametric Symporters A variant of KCC2 from patients with febrile seizures impairs neuronal Cl- extrusion and dendritic spine formation. http://purl.org/coar/resource_type/c_6501