Referenced in: none

Automatically associated channels: HCN1 , HCN2 , HCN3 , HCN4

Title: GENETIC ANALYSIS OF HYPERPOLARISATION-ACTIVATED CYCLIC NUCLEOTIDE-GATED CATION (HCN) CHANNELS IN SUDDEN UNEXPECTED DEATH IN EPILEPSY (SUDEP) CASES.

Authors: Emily Tu, Louise Waterhouse, Johan Duflou, Richard D Bagnall, Christopher Semsarian

Journal, date & volume: , 2011 May 25 , ,

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21615589

Abstract
Sudden unexpected death in epilepsy (SUDEP) is the most common epilepsy-related cause of death, yet the cause is unknown. Our previous studies suggest a role for arrhythmia-related ion channel genes in the pathogenesis of SUDEP. Hyperpolarization-activated cyclic nucleotide-gated cation (HCN1-4) channels are ion channels involved in generating spontaneous rhythmic activity in cardiac pacemaker and neuronal cells. This study sought to determine the role of pathogenic DNA variants in the HCN1-4 genes in a large SUDEP cohort collected from 1993 to 2009. Post-mortem DNA samples were amplified and analyzed for each HCN exon. Genetic analysis in 48 SUDEP cases (age range 12-82 years) identified six novel and three previously reported nonsynonymous (amino acid changing) variants in HCN1 (n = 1), HCN2 (n = 2), HCN3 (n = 2) and HCN4 (n = 4). The Phe738Cys and Pro802Ser variants in HCN2, and Gly973Arg in HCN4 were absent in control alleles and affecting highly conserved residues in the carboxyl-cytoplasmic tail region. Our results support a pathogenic link between the heart and brain in SUDEP, mediated by the HCN neuro-cardiac ion channel genes.