A novel de novo variant of GABRA1 causes increased sensitivity for GABA in vitro.

ABSTRACT: The GABRA1 gene encodes one of the most conserved and highly expressed subunits of the GABA_A receptor family. Variants in this gene are causatively implicated in different forms of epilepsy and also more severe epilepsy-related neurodevelopmental syndromes. Here we study functional consequences of a novel de novo missense GABRA1 variant, p.(Ala332Val), identified through exome sequencing in an individual affected by early-onset syndromic epileptic encephalopathy. The variant is localised within the transmembrane domain helix 3 (TM3) and in silico prediction algorithms suggested this variant to be likely pathogenic. In vitro assessment revealed unchanged protein levels, regular assembly and forward trafficking to the cell surface. On the functional level a significant left shift

SUBMITTER: Steudle F 

PROVIDER: S-EPMC7012862 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature