The analysis of whole exome sequencing (WES) data with bioinformatic tools for oligogenic diseases helped us to identify two major previously unreported pathogenetic variants: a maternally inherited missense variant (p.R4122H) in <i>HUWE1</i>, an ubiquitin protein ligase associated to X-linked intellectual disability and ASD; and a <i>de novo</i> stop variant (p.Q259X) in <i>TPH2</i>, encoding the tryptophan hydroxylase 2 enzyme involved in serotonin synthesis and associated with susceptibility to attention deficit-hyperactivity disorder (ADHD). The gene discussed is TPH2; the disease is X-linked intellectual disability.