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

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Item Type:	Article
Title:	Mutation analysis of the hyperpolarization-activated cyclic nucleotide-gated channels HCN1 and HCN2 in idiopathic generalized epilepsy
Creators Name:	Tang, B., Sander, T., Craven, K.B., Hempelmann, A. and Escayg, A.
Abstract:	Hyperpolarization-activated cyclic nucleotide-gated (HCN14) 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 conductancevoltage 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 casecontrol 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.
Keywords:	Hyperpolarization-activated cyclic nucleotide-gated channel, HCN1, HCN2, Idiopathic generalized epilepsy, IGE, Mutation analysis, Animals, Frogs
Source:	Neurobiology of Diseases
ISSN:	0969-9961
Publisher:	Elsevier
Volume:	29
Number:	1
Page Range:	59-70
Date:	January 2008
Official Publication:	https://doi.org/10.1016/j.nbd.2007.08.006
PubMed:	View item in PubMed

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