6 missense variants in the HCN1 gene, 5 of which were de novo in origin and were experimentally shown to alter channel properties, were identified in patients with epileptic encephalopathy; individuals with these variants had clinical features resembling those of Dravet syndrome with progression towards atypical absences, intellectual disability, and autistic features (Nava et al., 2014).
Molecular Function
The membrane protein encoded by this gene is a hyperpolarization-activated cation channel that contributes to the native pacemaker currents in heart and neurons. The encoded protein can homodimerize or heterodimerize with other pore-forming subunits to form a potassium channel. Detected in brain, in particular in amygdala and hippocampus.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
De novo mutations in HCN1 cause early infantile epileptic encephalopathy.
HCN1 missense mutation together with tm mutation (deletion) causes tremors and is a model for Essential Tremor. Inferior olive neurons mediate this phenotype.
References
Type
Title
Author, Year
Primary
Hcn1 is a tremorgenic genetic component in a rat model of essential tremor.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
TRM/Kyo rats were derived from a mutant showing body tremors and curled hair found in an outbred colony of Kyo:Wistar rats. Strain contains two spontaneous mutation: trm1 is a 240-kb deletion in chromosome 10 to which 13 genes have been mapped, and trm2 is a missense mutation in the Hcn1 gene (c. 1061 C>T, p. A354V). Control rats are WTC and TRMR (tremor-resistant).
Allele Type: Spontaneous mutation
Strain of Origin: Kyo:Wistar
Genetic Background: TRM/Kyo
ES Cell Line: Mutant ES Cell Line: Model Source: Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University
Description: Tremors appeared during movement. EMG recordings showed a synchronous association of EMG discharges with appearace of tremor. Tremor in TRM rats have a power peak frequency of 7-8 Hz.
Exp Paradigm: Tremor duration and intensity were estimated in each observation period. Recording of electromyograph activity was conducted under freely moving conditions.
Description: Fos expression was significantly elevated in TRM rats in several regions of the cerebral cortex, the medial tuberal hypothalamus, and the inferior olive.
Exp Paradigm: Immunohistochemistry
