About this item:

397 Views | 139 Downloads

Author Notes:

Correspondence: Andrew Escayg, Ph.D., Department of Human Genetics, Emory University, 615 Michael Street, Whitehead Building, Suite 301, Atlanta, Georgia 30322; E-mail: aescayg@genetics.emory.edu; Tel: (404) 712-8328; Fax: (404) 727-3949

Acknowledgments: We are grateful to the individuals and families who participated in this study.

We thank S.A. Siegelbaum for the HCN2 wild-type clone and Cheryl Strauss for critically reading the manuscript.

Subject:

Research Funding:

This study was supported by grants from the NIH (NS051834 to A.E.), the National Eye Institute (EY010329 to William N. Zagotta), the Deutsche Forschungsgemeinschaft (SA434/4-1 to T.S.), the German Federal Ministry of Education and Research (BMBF/NGFN2: 01GS0479 to T.S.), and the European Integrated Project EPICURE (EC contract number: LSH-CT-2006-037315 to T.S.).

Keywords:

  • Hyperpolarization-activated cyclic nucleotide-gated channel
  • HCN1
  • HCN2
  • idiopathic generalized epilepsy
  • IGE
  • mutation analysis

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

Tools:

Journal Title:

Neurobiology of Disease

Volume:

Volume 29, Number 1

Publisher:

, Pages 59-70

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Hyperpolarization-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.

Copyright information:

© 2007 Elsevier Inc. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).

Creative Commons License

Export to EndNote