A missense mutation in SLC6A1 associated with Lennox-Gastaut syndrome impairs GABA transporter 1 protein trafficking and function.

ABSTRACT:

Background

Mutations in SLC6A1 have been associated mainly with myoclonic atonic epilepsy (MAE) and intellectual disability. We identified a novel missense mutation in a patient with Lennox-Gastaut syndrome (LGS) characterized by severe seizures and developmental delay.

Methods

Exome Sequencing was performed in an epilepsy patient cohort. The impact of the mutation was evaluated by ³H γ-aminobutyric acid (GABA) uptake, structural modeling, live cell microscopy, cell surface biotinylation and a high-throughput assay flow cytometry in both neurons and non neuronal cells.

Results

We discovered a heterozygous missense mutation (c700G to A [pG234S) in the SLC6A1 encoding GABA transporter 1 (GAT-1). Structural modeling suggests the mutation destabilizes the globa

SUBMITTER: Cai K 

PROVIDER: S-EPMC6849469 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature