Augmented Currents of an HCN2 Variant in Patients with Febrile Seizure Syndromes
Leanne M Dibbens, Christopher A Reid, Bree Hodgson, Evan A Thomas, Alison M Phillips, Elena Gazina, Brett A Cromer, Alison L Clarke, Tallie Z Baram, Ingrid E Scheffer, Samuel F Berkovic, Steven Petrou
Annals of Neurology | WILEY | Published : 2010
The genetic architecture of common epilepsies is largely unknown. HCNs are excellent epilepsy candidate genes because of their fundamental neurophysiological roles. Screening in subjects with febrile seizures and genetic epilepsy with febrile seizures plus revealed that 2.4% carried a common triple proline deletion (delPPP) in HCN2 that was seen in only 0.2% of blood bank controls. Currents generated by mutant HCN2 channels were approximately 35% larger than those of controls; an effect revealed using automated electrophysiology and an appropriately powered sample size. This is the first association of HCN2 and familial epilepsy, demonstrating gain of function of HCN2 current as a potential ..View full abstract
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Awarded by National Health and Medical Research Council of Australia
Awarded by NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
This study was supported by the National Health and Medical Research Council of Australia (grants 400121 and 454655 to C.A.R. and S.P.) and an R. D. Wright Fellowship, University of Melbourne (C.A.R.).