A variant of KCC 2 from patients with febrile seizures impairs neuronal Cl − extrusion and dendritic spine formation
Copyright policy )A variant of KCC 2 from patients with febrile seizures impairs neuronal Cl − extrusion and dendritic spine formation
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.
- University of Helsinki Finland
- University of Münster Germany
- Florey Institute of Neuroscience and Mental Health Australia
- University of South Australia Australia
- University of Adelaide Australia
Models, Molecular, Protein Conformation, KCC2, Dendritic Spines, Blotting, Western, Molecular Sequence Data, Mutation, Missense, 610, genic intolerance, Statistics, Nonparametric, Seizures, Febrile, Mice, Chlorides, febrile seizures, Animals, Humans, Genetic Predisposition to Disease, Amino Acid Sequence, Rats, Wistar, Biochemistry, cell and molecular biology, Neurons, Mice, Inbred ICR, Symporters, Scientific Reports, Australia, dendritic spines, Pedigree, Rats, Microscopy, Fluorescence, mutation
Models, Molecular, Protein Conformation, KCC2, Dendritic Spines, Blotting, Western, Molecular Sequence Data, Mutation, Missense, 610, genic intolerance, Statistics, Nonparametric, Seizures, Febrile, Mice, Chlorides, febrile seizures, Animals, Humans, Genetic Predisposition to Disease, Amino Acid Sequence, Rats, Wistar, Biochemistry, cell and molecular biology, Neurons, Mice, Inbred ICR, Symporters, Scientific Reports, Australia, dendritic spines, Pedigree, Rats, Microscopy, Fluorescence, mutation
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