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https://ahro.austin.org.au/austinjspui/handle/1/12142| Title: | A variant of KCC2 from patients with febrile seizures impairs neuronal Cl- extrusion and dendritic spine formation. | Austin Authors: | Puskarjov, Martin;Seja, Patricia;Heron, Sarah E;Williams, Tristiana C;Ahmad, Faraz;Iona, Xenia;Oliver, Karen L;Grinton, Bronwyn E;Vutskits, Laszlo;Scheffer, Ingrid E ;Petrou, Steven;Blaesse, Peter;Dibbens, Leanne M;Berkovic, Samuel F ;Kaila, Kai | Affiliation: | Florey Institute of Neuroscience and Mental Health and the Center for Neural Engineering, The University of Melbourne, Parkville, Victoria, Australia Epilepsy Research Program, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia Department of Medicine, Epilepsy Research Center, The University of Melbourne Austin Health, Melbourne Victoria, Australia Epilepsy Research Program, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia Sansom Institute for Health Research, University of South Australia, Adelaide SA, Australia Department of Paediatrics, Florey Institute, Royal Children's Hospital The University of Melbourne, Melbourne, Victoria, Australia Department of Medicine, Epilepsy Research Center, The University of Melbourne Austin Health, Melbourne Victoria, Australia Department of Paediatrics, Florey Institute, Royal Children's Hospital The University of Melbourne, Melbourne, Victoria, Australia Department of Biosciences, University of Helsinki, Helsinki, Finland Neuroscience Center, University of Helsinki, Helsinki, Finland. Department of Anesthesiology, Pharmacology and Intensive Care, University Hospital of Geneva, Geneva, Switzerland. Department of Biosciences, University of Helsinki, Helsinki, Finland Institute of Physiology I, Westfälische Wilhelms-University Münster, Münster, Germany. Department of Biosciences, University of Helsinki, Helsinki, Finland Neuroscience Center, University of Helsinki, Helsinki, Finland Kai.Kaila@Helsinki.fi. |
Issue Date: | 24-Mar-2014 | Publication information: | Embo Reports 2014; 15(6): 723-9 | Abstract: | 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. | Gov't Doc #: | 24668262 | URI: | https://ahro.austin.org.au/austinjspui/handle/1/12142 | DOI: | 10.1002/embr.201438749 | Journal: | EMBO reports | URL: | https://pubmed.ncbi.nlm.nih.gov/24668262 | Type: | Journal Article | Subjects: | KCC2 dendritic spines febrile seizures genic intolerance mutation Amino Acid Sequence Animals Australia Blotting, Western Chlorides.metabolism Dendritic Spines.genetics.pathology Genetic Predisposition to Disease.genetics Humans Mice Mice, Inbred ICR Microscopy, Fluorescence Models, Molecular Molecular Sequence Data Mutation, Missense.genetics Neurons.metabolism Pedigree Protein Conformation Rats Rats, Wistar Seizures, Febrile.genetics Statistics, Nonparametric Symporters.genetics.metabolism |
| Appears in Collections: | Journal articles |
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