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Augmented currents of an HCN2 variant in patients with febrile seizure syndromes
Author(s) -
Dibbens Leanne M.,
Reid Christopher A.,
Hodgson Bree,
Thomas Evan A.,
Phillips Alison M.,
Gazina Elena,
Cromer Brett A.,
Clarke Alison L.,
Baram Tallie Z.,
Scheffer Ingrid E.,
Berkovic Samuel F.,
Petrou Steven
Publication year - 2010
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.21909
Subject(s) - epilepsy , electroencephalography , neurophysiology , generalized epilepsy , genetic architecture , neuroscience , medicine , electrophysiology , febrile seizure , bioinformatics , psychology , biology , genetics , gene , phenotype
The genetic architecture of common epilepsies is largely unknown. HCN s 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 ∼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 contributor to polygenic epilepsy. ANN NEUROL 2010;67:542–546