Ultra-Rare Genetic Variation in the Epilepsies : A Whole-Exome Sequencing Study of 17,606 Individuals

Sequencing-based studies have identified novel risk genes associated with severe epilepsies and revealed an excess of rare deleterious variation in less-severe forms of epilepsy. To identify the shared and distinct ultra-rare genetic risk factors for different types of epilepsies, we performed a whole-exome sequencing (WES) analysis of 9,170 epilepsy-affected individuals and 8,436 controls of European ancestry. We focused on three phenotypic groups: severe developmental and epileptic encephalopathies (DEEs), genetic generalized epilepsy (GGE), and non-acquired focal epilepsy (NAFE). We observed that compared to controls, individuals with any type of epilepsy carried an excess of ultra-rare, deleterious variants in constrained genes and in genes previously associated with epilepsy; we saw the strongest enrichment in individuals with DEEs and the least strong in individuals with NAFE. Moreover, we found that inhibitory GABA(A) receptor genes were enriched for missense variants across all three classes of epilepsy, whereas no enrichment was seen in excitatory receptor genes. The larger gene groups for the GABAergic pathway or cation channels also showed a significant mutational burden in DEEs and GGE. Although no single gene surpassed exome-wide significance among individuals with GGE or NAFE, highly constrained genes and genes encoding ion channels were among the lead associations; such genes included CACNAIG, EEF1A2, and GABRG2 for GGE and LGI1, TRIM3, and GABRG2 for NAFE. Our study, the largest epilepsy WES study to date, confirms a convergence in the genetics of severe and less-severe epilepsies associated with ultra-rare coding variation, and it highlights a ubiquitous role for GABAergic inhibition in epilepsy etiology.Peer reviewe

Modifying of Cotton Fabric Surface with Nano-ZnO Multilayer Films by Layer-by-Layer Deposition Method

<p>Abstract</p> <p>ZnO nanoparticle&#8211;based multilayer nanocomposite films were fabricated on cationized woven cotton fabrics via layer-by-layer molecular self-assembly technique. For cationic surface charge, cotton fabrics were pretreated with 2,3-epoxypropyltrimethylammonium chloride (EP3MAC) by pad-batch method. XPS and SEM were used to examine the deposited nano-ZnO multilayer films on the cotton fabrics. The nano-ZnO films deposited on cotton fabrics exhibited excellent antimicrobial activity against <it>Staphylococcus aureus</it> bacteria. The results also showed that the coated fabrics with nano-ZnO multilayer films enhanced the protection of cotton fabrics from UV radiation. Physical tests (tensile strength of weft and warp yarns, air permeability and whiteness values) were performed on the fabrics before and after the treatment with ZnO nanoparticles to evaluate the effect of layer-by-layer (LbL) process on cotton fabrics properties.</p