AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca 2+ -impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission.

Background: Tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND) have unique, individual patterns that pose significant challenges for diagnosis, psycho-education, and intervention planning. A recent study suggested that it may be feasible to use TAND Checklist data and data-driven methods to generate natural TAND clusters. However, the study had a small sample size and data from only two countries. Here, we investigated the replicability of identifying natural TAND clusters from a larger and more diverse sample from the TOSCA study. Methods: As part of the TOSCA international TSC registry study, this embedded research project collected TAND Checklist data from individuals with TSC. Correlation coefficients were calculated for TAND variables to generate a correlation matrix. Hierarchical cluster and factor analysis methods were used for data reduction and identification of natural TAND clusters.

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Objective: Although seizures are more common in the neonatal period than in any other stage of childhood, those in preterm neonates are still poorly described. The aim of this study was to assess electro-clinical characteristics of seizures occurring before a corrected age of 40 weeks in neonates born prematurely. Method Conclusion:Ictal EEG features undergo changes depending on corrected age. Most seizures are subclinical, thus EEG is essential for diagnosis.Significance: Relating ictal EEG pattern to corrected age can improve diagnosis and ultimately management.Key words: preterm, neonate, epileptic seizures, electroencephalography Highlights:Most seizures in preterm newborns are subclinical, thus EEG is required for diagnosis.Seizures in preterm neonates have smaller regions of onset and propagate less frequently.Ictal EEG features undergo changes depending on corrected age likely reflecting maturational changes.3

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