Autism and intestinal permeability: bioinformatics selection of candidate genes target

AUTISM is considered a complex multifactorial disorder with genetic base, but causative genetic variations involve only a limited number of patients (15-40%), also evidenced by the risk familiarity. As hundreds of gene variants were found in only a subset of patients, the best model for ASD etiology would be OLIGOGENIC (HEREDITY + DE NOVO MUTATIONS) with an ENVIRONMENTAL contribution indeed a large number of genes confer risk to ASD as well as a large number of environmental factors have been proposed to interact with these genes. Moreover autistic patients often suffer from several comorbidities, among which, GASTROINTESTINAL (GI) DISORDERS with intestinal pathogen overgrowth and gut permeability have 60% prevalence and correlates with autistic symptom severity. These evidences have suggested that GI disorders alter the so called "GUT-BRAIN AXIS", or even MICROBIOTA-GUT- BRAIN EQUILIBRIUM and trigger the disease in genetically predisposed children. Perturbations of the gut microbiota alter the INTESTINAL PERMEABILITY and INFLAMMATORY SYSTEM thus playing a deleterious role IN NEURODEVELOPMENT as evidenced by inflammation condition in severe ASD patients with GI disorders and dysbiosis. Our aim was to identify the GENETIC PREDISPOSITION TO GUT PERMEABILITY leading to ABSORPTION OF ENVIRONMENTAL RISK FACTORS that, in turn, trigger the disease. Starting from these findings we will focus on the four underlined proteins among the 17 selected, involved in intestinal permeability in order to define the role of the relative mutations on the protein function and in ASD pathogenesis