Interestingly, inborn deletion of thalamic reticular nucleus-enriched, human childhood absence epilepsy-linked gene Cacna1h in iKOp/q mice reduces thalamic reticular nucleus burst firing and promotes rather than reduces seizure, indicating an epileptogenic role for loss of function Cacna1h gene variants reported in human childhood absence epilepsy cases.
Mutations in GABRB3 have been increasingly recognized as a major cause for severe paediatric epilepsy syndromes such as Lennox-Gastaut syndrome, Dravet syndrome and infantile spasms with intellectual disability as well as relatively mild epilepsy syndromes such as childhood absence epilepsy.
To determine whether common polymorphisms in CACNA1G, CACNA1H, CACNA1I, and ABCB1 are associated with differential short-term seizure outcome in childhood absence epilepsy (CAE).
Previous studies reported that SNPs at the 5' regulatory region of GABRB3 could regulate GABRB3 gene expression and associated with childhood absence epilepsy (CAE).
GABRB3 mutation, G32R, associated with childhood absence epilepsy alters α1β3γ2L γ-aminobutyric acid type A (GABAA) receptor expression and channel gating.
Mutations in inhibitory GABAA receptor subunit genes (GABRA1, GABRB3, GABRG2 and GABRD) have been associated with genetic epilepsy syndromes including childhood absence epilepsy (CAE), juvenile myoclonic epilepsy (JME), pure febrile seizures (FS), generalized epilepsy with febrile seizures plus (GEFS+), and Dravet syndrome (DS)/severe myoclonic epilepsy in infancy (SMEI).
Our research provides new evidence to further support the hypothesis that CACNA1H may be an important susceptibility gene for CAE in the Chinese Han population.
CACNA1H is a human gene encoding Ca(v)3.2 low-voltage-activated, T-type calcium channels associated with bursting behavior in neurons and has been linked to more than 30 mutations apparently predisposing to childhood absence epilepsy (CAE) and other idiopathic generalized epilepsies (IGEs).
These results suggest that CACNA1H is a susceptibility gene that contributes to the development of polygenic disorders characterized by thalamocortical dysrhythmia, such as CAE.
The object of this study was to investigate whether or not CAE is associated with the gene encoding the gamma-aminobutyric acid (GABA) type-A receptor subunits alpha5 (GABRA5) and beta3 (GABRB3) in a Chinese population.
The object of the present study was to test association between CAE and the genes encoding the gamma-aminobutyric acid (GABA) type-A receptor subunits alpha 5 (GABRA5) and beta 3 (GABRB3) located on the long arm of chromosome 15 (15q11-q13).
To confirm whether the JRK/JH8 gene is responsible for ECA1, we performed mutational analyses in the coding region of JRK/JH8 in two CAE families mapped on 8q24, using heteroduplex and direct sequencing methods.