Pathophysiology of and therapeutic options for a GABRA1 variant linked to epileptic encephalopathy.

ABSTRACT: We report the identification of a de novo GABRA1 (R214C) variant in a child with epileptic encephalopathy (EE), describe its functional characterization and pathophysiology, and evaluate its potential therapeutic options. The GABRA1 (R214C) variant was identified using whole exome sequencing, and the pathogenic effect of this mutation was investigated by comparing wild-type (WT) α1 and R214C α1 GABA_A receptor-expressing HEK cells. GABA-evoked currents in these cells were recorded using whole-cell, outside-out macro-patch and cell-attached single-channel patch-clamp recordings. Changes to surface and total protein expression levels of WT α1 and R214C α1 were quantified using surface biotinylation assay and western blotting, respectively. Finally, potential therapeutic options wer

SUBMITTER: Bai YF 

PROVIDER: S-EPMC6842544 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature