Mutation analysis of the hyperpolarization-activated cyclic nucleotide-gated channels HCN1 and HCN2 in idiopathic generalized epilepsy

被引：54

作者：

Tang, Bin ^{[1
]}

Sander, Thomas ^{[2
,3
]}

Craven, Kimberley B. ^{[4
]}

Hempelmann, Anne ^{[2
]}

Escayg, Andrew ^{[1
]}

机构：

[1] Emory Univ, Dept Human Genet, Atlanta, GA 30322 USA

[2] Max Delbruck Ctr Mol Med, Berlin, Germany

[3] Humboldt Univ, Epilepsy Genet Grp, Dept Neurol, Charite Univ Med, Berlin, Germany

[4] Univ Washington, Dept Phys & Biophys, Seattle, WA 98195 USA

来源：

NEUROBIOLOGY OF DISEASE | 2008年 / 29卷 / 01期

关键词：

hyperpolarization-activated cyclic nucleotide-gated channel; HCN1; HCN2; idiopathic generalized epilepsy; IGE; mutation analysis;

D O I：

10.1016/j.nbd.2007.08.006

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Hyper polarization-activated cyclic nucleotide-gated (HCN1-4) channels play an important role in the regulation of neuronal rhythmicity. In the present study we describe the mutation analysis of HCN1 and HCN2 in 84 unrelated patients with idiopathic generalized epilepsy (IGE). Several functional variants were identified including the amino acid substitution R527Q in HCN2 exon 5. HCN2 channels containing the R527Q variant demonstrated a trend towards a decreased slope of the conductance-voltage relation. We also identified a variant in the splice donor site of HCN2 exon 5 that results in the formation of a cryptic splice donor. In HCN1, the amino acid substitution A881T was identified in one sporadic IGE patient but was not observed in 510 controls. Seven variants were examined further in a case-control association study consisting of a larger cohort of IGE patients. Further studies are warranted to more clearly establish the contribution of HCN1 and HCN2 dysfunction to the genetic variance of common IGE syndromes. (c) 2007 Elsevier Inc. All rights reserved.

引用

页码：59 / 70

页数：12