The γ2(R43Q) mutation linked to epilepsy affects GABAA receptor internalization

Idiopathic Absence Epilepsies (IAE) are complex syndromes with a strong genetic component. Childhood absence Epilepsy (CAE) is a common form of IAE, affecting children between the age of 3 and 8 years old and that has been associated with mutations in the GABAA receptor. Particularly, a R43Q mutation on the 2 subunit, which impairs GABAA receptor function, has been clearly linked to CAE in animal models and patients. The same mutation has also been linked to febrile seizures, another epileptic syndrome, characterized by a later onset than CAE. GABA is the major inhibitory neurotransmitter in the brain, and dysregulation of GABA synaptic transmission can have drastic effects on neuronal excitability. It is therefore not surprising that mutations impairing the activity of GABAA receptors are involved in epileptic pathologies. This research highlight describes our latest study, dissecting the effect of the R43Q mutation on the receptor’s function.