A variant of KCC2 from patients with febrile seizures impairs neuronal Cl- extrusion and dendritic spine formation.

2014-03-24

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

Journal Article

10.1002/embr.201438749

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.

link

Embo Reports 2014; 15(6): 723-9

EMBO reports