Autism spectrum disorder and intellectual disability (ASD/ID) are severe neurodevelopmental conditions withearly childhood onset. Advances in genetics have illustrated that ASD/ID represent a spectrum of raredisorders and that mutations in hundreds of genes may result in susceptibility to ASD/ID. This heterogeneityrepresents significant challenges but at the same time unique opportunities for research in the field ofASD/ID. Many of the genes implicated in ASD/ID appear to converge on a few common pathways,suggesting that there may be a common dysfunction at the cellular or systems level. Deeper understandingof the shared pathophysiology of these diseases may serve as gateways for understanding mechanisms ofother causes of ASD/ID and for shared treatment possibilities. Here we focus of three well-establishedgenetic syndromes that are associated with high penetrance for ASD/ID: TSC1/2, PTEN and SHANKSmutations. Specific aims for TSC are: 1) characterize the developmental phenotype of ASD and ID in a largecohort of pediatric patients with TSC; 2) identify biomarkers using advanced MR imaging; 3) establishinfrastructure for the collection and storage of human bio-specimens, including genetic material, from TSCpatients and their family members with ASD. Specific aims for PTEN are: 1) determine cross-sectional andlongitudinal medical, behavioral, and cognitive differences between PTEN ASD and other groups; 2) identifycognitive, neural systems, and molecular biomarkers specific to PTEN ASD; 3) create and maintain abiorepository and linked phenotypic database for PTEN ASD. Specific aims for SHANKS are: 1) characterizePMS using standardized medical, behavioral, and cognitive measures and to track the natural history of thesyndrome using repeated longitudinal assessments; 2) identify biomarkers using advanced MR imaging; S)identify genetic factors which contribute to diverse phenotypes in patients with PMS. As detailed in theResources sections, this Consortium involves experienced physician-researchers from premier academicinstitutions with strong institutional support, impressive mentors for training of future physician-researchers,and long-standing connections to patient advocacy organizations with extensive recruitment networks.
Interagency Autism Coordinating Committee (IACC)
Autism Research Database (AFD)
