Epileptic encephalopathy de novo GABRB mutations impair γ-aminobutyric acid type A receptor function.

ABSTRACT:

Objective

The Epi4K Consortium recently identified 4 de novo mutations in the γ-aminobutyric acid type A (GABA_A ) receptor β3 subunit gene GABRB3 and 1 in the β1 subunit gene GABRB1 in children with one of the epileptic encephalopathies (EEs) Lennox-Gastaut syndrome (LGS) and infantile spasms (IS). Because the etiology of EEs is often unknown, we determined the impact of GABRB mutations on GABA_A receptor function and biogenesis.

Methods

GABA_A receptor α1 and γ2L subunits were coexpressed with wild-type and/or mutant β3 or β1 subunits in HEK 293T cells. Currents were measured using whole cell and single channel patch clamp techniques. Surface and total expression levels were measured using flow cytometry. Potential structural perturbations in

SUBMITTER: Janve VS 

PROVIDER: S-EPMC5014730 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature