A Variant of KCC2 from Patients with Febrile Seizures Impairs Neuronal Cl- Extrusion and Dendritic Spine Formation

Overview

Journal EMBO Rep

Specialty Molecular Biology

Date 2014 Mar 27

PMID 24668262

Citations 86

Authors

Martin Puskarjov

Patricia Seja

Sarah E Heron

Tristiana C Williams

Faraz Ahmad

Xenia Iona

Karen L Oliver

Bronwyn E Grinton

Laszlo Vutskits

Ingrid E Scheffer

Steven Petrou

Peter Blaesse

Leanne M Dibbens

Samuel F Berkovic

Kai Kaila

Affiliations

Soon will be listed here.

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.

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