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

Neurobiology of Disease

Kimberley B. Craven¹  Bin Tang²  Anne Hempelmann³  Andrew Escayg⁴  Thomas Sander⁴ 

[1] Epilepsy Genetics Group, Department of Neurology, Charité University Medicine, Humboldt University of Berlin, Berlin, Germany;Department of Human Genetics, Emory University, 615 Michael Street, Whitehead Building, Suite 301, Atlanta, GA 30322, USA;Department of Physiology and Biophysics, University of Washington, Seattle, USA;Max Delbruck Center for Molecular Medicine, Berlin, Germany;

关键词: Hyperpolarization-activated cyclic nucleotide-gated channel;    HCN1;    HCN2;    Idiopathic generalized epilepsy;    IGE;    Mutation analysis;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown