Exploring genetic bases of Intellectual disability and Autism: from Exome Sequencing on

Intellectual disability and autism spectrum disorder are various conditions with features often including status epilepticus, attention deficit hyperactivity disorder, craniofacial dysmorphisms, symptoms overlapping to many neurodevelopmental disorders. A net discernment between these conditions appears tricky, and a clinical evolution for many pathologies has been observed from childhood to adulthood presenting symptoms common to different pathologies (e.g. KBG syndrome, Cornelia de Lange, Noonan syndrome…). Whole-Exome sequencing has recently been recommended as a first-tier diagnostic tool in the investigation of the genetic defects of neurodevelopmental disorders, being a valid tool to cope with the wide clinical and locus heterogeneity underlying the pathogenesis of intellectual disability and autism. Its application in the research field has elucidated novel altered pathways as well as it has raised the possibility to investigate that part of the genome still unknown. Moreover, thanks to the support of experimental evidence, mutation specific mechanisms have been unrevealed for the genes of intellectual disability and autism. We introduce a site-specific mutagenesis approach on the NLGN4X gene, which highlights a likely gain of function mechanism for a series of missense variants.