Clinical School (Austin Health) - Research Publications

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

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 (WILEY-BLACKWELL, 2014-06)

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.
Does variation in NIPA2 contribute to genetic generalized epilepsy?

Hildebrand, MS ; Damiano, JA ; Mullen, SA ; Bellows, ST ; Scheffer, IE ; Berkovic, SF (SPRINGER, 2014-05)