14-05-2020 | Letter to the Editor
Case Report: Is Catatonia a Clinical Feature of the Natural Progression of NLGN2-Related Neurodevelopmental Disorder?
Gepubliceerd in: Journal of Autism and Developmental Disorders | Uitgave 1/2021Log in om toegang te krijgen
ExcerptAutism Spectrum Disorder (ASD) is a developmental disorder characterized by impairments in social communication along with restrictive interests and repetitive behaviors that are typically present early in development. Genetics has a key role in the etiology of ASD, while environmental factors interplay at the molecular level contributing to changes in neuronal development, growth of the brain, and synaptic connectivity. Genes responsible for protein function within synapses are of particular interest in the pathology of ASD. Imbalances in excitatory-inhibitory signaling at the synaptic level are thought to contribute to destabilization of neural processing early in development leading to the ASD phenotype (Howell and Smith 2019). Neurexins and neuroligins are two families of transmembrane synaptic cell adhesion molecule (SCAM) proteins located at presynaptic and postsynaptic membranes respectively. These proteins function to induce synapse formation and maturation. SH3 and multiple ankyrin repeat domains (SHANK) proteins (SHANK1, SHANK2, SHANK3) indirectly tether SCAM proteins and glutamate receptor proteins (Fig. 1a, b) creating a functional complex necessary for optimal synaptic signaling (Howell and Smith 2019). Variants in genes in these pathways have been linked to ASD (Cao and Tabuchi 2017) and SCAM and SHANK knock-out mice models show autistic behavioral phenotypes (Baig et al. 2017).