GABA|[sol]|Glutamate synaptic pathways targeted by integrative genomic and electrophysiological explorations distinguish autism from intellectual disability

摘要: Phenotypic and genetic heterogeneity is predominant in autism spectrum disorders (ASD), for which the molecular pathophysiological bases are still unclear. Significant comorbidity overlap between ASD other neurodevelopmental also well established. However, little understood regarding frequent observation of a wide phenotypic associated with deleterious mutations affecting single gene even within multiplex families. We performed clinical, neurophysiological (in vivo electroencephalography—auditory-evoked related potentials) (whole-exome sequencing) follow-up analysis two families known NLGN4X (either truncating or overexpressing) present individuals and/or intellectual disability (ID). Complete evaluation pedigrees showed common specific autistic behavioural features patterns (abnormal MisMatch Negativity response to auditory change) that were absent healthy parents as family members isolated ID. Whole-exome sequencing patients from each identified second rare inherited variant, either GLRB ANK3 genes encoding interacting proteins expressed inhibitory excitatory synapses, respectively. The GRLB relatives ID control databases. In summary, our findings provide evidence double-hit model focused on excitatory/inhibitory synapses ASD, not found ID, an atypical pattern linked predictive coding.