Phelan-McDermid Syndrome (PMDS) is a progressive neurodevelopmental disorder, characterized by hypotonia, global developmental delay, severely impaired to absent speech, intellectual disability, and autism spectrum disorders (ASDs). PMDS is a genetic disorder caused by the micro deletions in the pretelomeric region of chromosome 22. The goal of this project is to identify cellular and molecular abnormalities associated with neurological defects in patients with PMDS and ASDs. As starting material we use skin cells collected from PMDS patients. We reprogram skin cells into induced pluripotent stem cells (iPSCs) (which are cells that have the potential to differentiate into several different types of cells,) and then iPSCs into neurons. Studying properties of iPSCs-derived neurons from patients and controls, we are aiming to find the original genetically-based source of the problems at cellular and molecular levels. Results of this research will substantially advance our current understanding of neurobiology associated with PMDS and ASDs in humans, and the role of different genes in the development of specific cellular abnormalities. In addition, this project will provide valuable information on new therapeutic targets for future pharmacological intervention to reverse neurological defects in patients with PMDS and ASDs.