Functional characterization of epilepsy associated GABRG2 mutations

Abstract

Mutations in inhibitory GABAA receptor γ2 subunit gene, GABRG2, have been associated with genetic epilepsy syndromes including childhood absence epilepsy (CAE), pure febrile seizures (FS), generalized epilepsy with febrile seizures plus (GEFS+), and Dravet syndrome (DS). This dissertation elucidated the function of three epilepsy associated GABRG2 mutations, IVS6+2T->G, Q40X, and S443delC, which are found in both GABRG2 gene coding and non-coding regions. They impairing GABAA receptor biogenesis by multiple mechanisms including reducing subunit mRNA stability, impairing subunit folding, stability, or oligomerization and by inhibiting receptor trafficking. Aminoglycosides treatment could treat seizures induced by GABRG2(Q40X) mutation, but the treatment for epilepsies induced by other GABRG2 mutation is under investigation.