Augmented Currents of an HCN2 Variant in Patients with Febrile Seizure Syndromes

被引：98

作者：

Dibbens, Leanne M. ^{[2
,3
]}

Reid, Christopher A. ^{[4
]}

Hodgson, Bree ^{[2
,3
]}

Thomas, Evan A. ^{[4
]}

Phillips, Alison M. ^{[4
]}

Gazina, Elena ^{[4
]}

Cromer, Brett A. ^{[4
]}

Clarke, Alison L. ^{[4
]}

Baram, Tallie Z. ^{[5
,6
]}

Scheffer, Ingrid E. ^{[7
,8
]}

Berkovic, Samuel F. ^{[8
]}

Petrou, Steven ^{[1
,4
]}

机构：

[1] Univ Melbourne, Howard Florey Inst, Ctr Neurosci, Parkville, Vic 3010, Australia

[2] SA Pathol Womens & Childrens Hosp, Epilepsy Res Program, Adelaide, SA, Australia

[3] Univ Adelaide, Sch Paediat & Reprod Hlth, Adelaide, SA, Australia

[4] Univ Melbourne, Florey Neurosci Inst, Parkville, Vic 3010, Australia

[5] Univ Calif Irvine, Dept Pediat, Irvine, CA 92717 USA

[6] Univ Calif Irvine, Dept Anat Neurobiol, Irvine, CA 92717 USA

[7] Univ Melbourne, Royal Childrens Hosp, Dept Paediat, Melbourne, Vic, Australia

[8] Univ Melbourne, Dept Med, Heidelberg West, Vic, Australia

来源：

ANNALS OF NEUROLOGY | 2010年 / 67卷 / 04期

基金：

英国医学研究理事会;

关键词：

GENERALIZED EPILEPSY; H-CHANNELS; I-H; EXPRESSION; MODEL; INHIBITION; MUTATION;

D O I：

10.1002/ana.21909

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

100204 [神经病学];

摘要：

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 similar to 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

引用

页码：542 / 546

页数：5

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