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 global protein conformation. With transient expression of enhanced yellow fluorescence protein (YFP) tagged rat GAT-1 cDNAs, we demonstrated that the mutant GAT-1(G234S) transporter had reduced total protein expression in both rat cortical neurons and HEK 293T cells. With a high-throughput flow cytometry assay and live cell surface biotinylation, we demonstrated that the mutant GAT-1(G234S) had reduced cell surface expression. 3H radioactive labeling GABA uptake assay in HeLa cells indicated a reduced function of the mutant GAT-1(G234S). Conclusions: This mutation caused instability of the mutant transporter protein, which resulted in reduced cell surface and total protein levels. The mutation also caused reduced GABA uptake in addition to reduced protein expression, leading to reduced GABA clearance, and altered GABAergic signaling in the brain. The impaired trafficking and reduced GABA uptake function may explain the epilepsy phenotype in the patient.

Recently SnSe compound was reported to have a peak thermoelectric figure-of-merit (ZT) of ~2.62 at 923 K, but the ZT values at temperatures below 750 K are relatively low. In this work, the electronic structures of SnSe are calculated using the density functional theory, and the electro-and thermo-transport properties upon carrier density are evaluated by the semi-classic Boltzmann transport theory, revealing that the calculated ZT values along the a-and c-axes below 675 K are in 10 agreement with reported values, but that along the b-axis can be as high as 2.57 by optimizing the carrier concentration to n ~ 3.6×10 19 cm -3 . It is suggested that a mixed ionic-covalent bonding and heavy-light band overlapping near the valence band are the reasons for the higher thermoelectric performance.

No abstract

Objective: To analyze the clinical features in children with anti-NMDAR encephalitis combined with myelin oligodendrocyte glycoprotein antibody (MOG ab).