Epilepsy
|
0.400 |
Biomarker
|
disease |
BEFREE |
Deficiency in HCN1 function is associated with sick sinus syndrome in mice and epilepsy in humans.
|
31292305 |
2020 |
Epilepsy
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
According to these results and data from literature, alteration of HCN1 channel function seems to play a major role in epilepsy, but also dysfunctional HCN2 and HCN4 channels can predispose to the development of the disease.
|
30986657 |
2019 |
Epilepsy
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Electrophysiological analysis in heterologous expression model (CHO cells) and in neurons revealed that L157V is a loss-of-function, dominant negative mutation causing reduced HCN1 contribution to net inward current and responsible for an increased neuronal firing rate and excitability, potentially predisposing to epilepsy.
|
29936235 |
2018 |
Epilepsy
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
To delineate HCN1-related disorders and investigate genotype-phenotype correlations further, we assembled a cohort of 33 unpublished patients with novel pathogenic or likely pathogenic variants: 19 probands carrying 14 different de novo mutations and four families with dominantly inherited variants segregating with epilepsy in 14 individuals, but not penetrant in six additional individuals.
|
30351409 |
2018 |
Epilepsy
|
0.400 |
Biomarker
|
disease |
BEFREE |
Studies in rat models have shown that the Hcn1 gene has a key role in epilepsy, but clinical evidence implicating HCN1 mutations in human epilepsy is lacking.
|
24747641 |
2014 |
Epilepsy
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Spike-and-wave discharge mediated reduction in hippocampal HCN1 channel function associates with learning deficits in a genetic mouse model of epilepsy.
|
24368169 |
2014 |
Epilepsy
|
0.400 |
Biomarker
|
disease |
BEFREE |
Taken together, HCN1 is proposed to play an important role in the molecular linkage between epileptic seizures and Aβ generation, and in the aggravation of sporadic AD.
|
23034178 |
2012 |
Epilepsy
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
However, only recently have genetic studies demonstrated sequence variation in HCN1 and HCN2 genes associated with human epilepsy.
|
21615728 |
2012 |
Epilepsy
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
By screening families with epilepsy for mutations in Hcn1 and Hcn2 genes, we found a recessive loss-of-function point mutation in the gene coding for the HCN2 channel in a patient with sporadic idiopathic generalized epilepsy.
|
22131395 |
2011 |
Epilepsy
|
0.400 |
Biomarker
|
disease |
BEFREE |
While full evidence for neuronal HCN channelopathies is not yet available, several indications point to a link between temporal lobe and absence epilepsies and altered distribution of HCN1/HCN2 isoforms.
|
20213494 |
2010 |
Epilepsy
|
0.400 |
Biomarker
|
disease |
BEFREE |
Early treatment with ethosuximide blocked changes in the expression of ion channels Nav1.1, Nav1.6, and HCN1 normally associated with epilepsy in this model.
|
18070091 |
2008 |
Epilepsy
|
0.400 |
Biomarker
|
disease |
CTD_human |
In contrast, HCN1 mRNA expression over the GC layer and in individual GCs from epileptic hippocampus was markedly increased once GC neuronal density was reduced by >50%.
|
12890777 |
2003 |