title: Synaptic dysfunction in neurodevelopmental disorders associated with autism and intellectual disabilities.
abstract: The discovery of the genetic causes of syndromic autism spectrum disorders and intellectual disabilities has greatly informed our understanding of the molecular pathways critical for normal synaptic function. The top-down approaches using human phenotypes and genetics helped identify causative genes and uncovered the broad spectrum of neuropsychiatric features that can result from various mutations in the same gene. Importantly, the human studies unveiled the exquisite sensitivity of cognitive function to precise levels of many diverse proteins. Bottom-up approaches applying molecular, biochemical, and neurophysiological studies to genetic models of these disorders revealed unsuspected pathogenic mechanisms and identified potential therapeutic targets. Moreover, studies in model organisms showed that symptoms of these devastating disorders can be reversed, which brings hope that affected individuals might benefit from interventions even after symptoms set in. Scientists predict that insights gained from studying these rare syndromic disorders will have an impact on the more common nonsyndromic autism and mild cognitive deficits.
authors.affiliation: Howard Hughes Medical Institute, The Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, Texas 77030, USA.hzoghbi@bcm.edu; mbear@mit.edu
authors.forename: Huda Y
authors.initials: HY
authors.lastname: Zoghbi
authors.forename: Mark F
authors.initials: MF
authors.lastname: Bear
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics* / Q000503:physiopathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics* / Q000503:physiopathology; D009435:Synaptic Transmission / Q000235:genetics
chemical_list: D015816:Cell Adhesion Molecules, Neuronal