Autism has several phenotypic features in common with the neurodevelopmental disorders Rett syndrome (RTT) and Angelman syndrome (AS). RTT is a disorder caused by mutations in the gene MECP2, and AS is a disorder caused by maternal deficiency of chromosome 15q11-13. Because MECP2 mutations have been found in a few patients diagnosed with AS and autism and 15q11-13 duplications are found in autism, these three distinct genetic syndromes may have overlapping pathologies. This research proposal focuses on the hypothesis that MECP2 regulates gene expression in the 15q11-13 region, and that aberrations in this regulatory pathway may contribute to phenotypic features of autism spectrum disorders. Using mouse and human brain tissue, these studies aim to uncover important mechanistic similarities between the overlapping neurodevelopmental disorders RTT, AS, and autism. The successful completion of these studies should yield findings to help develop better diagnostic and treatment modalities for autism spectrum disorders.