title: The genetic and neurobiologic compass points toward common signaling dysfunctions in autism spectrum disorders.
abstract: Autism spectrum disorder (ASD) is a common neurodevelopmental disorder with high heritability. Here, we discuss data supporting the view that there are at least two distinct genetic etiologies for ASD: rare, private (de novo) single gene mutations that may have a large effect in causing ASD; and inherited, common functional variants of a combination of genes, each having a small to moderate effect in increasing ASD risk. It also is possible that a combination of the two mechanisms may occur in some individuals with ASD. We further discuss evidence from individuals with a number of different neurodevelopmental syndromes, in which there is a high prevalence of ASD, that some private mutations and common variants converge on dysfunctional ERK and PI3K signaling, which negatively impacts neurodevelopmental events regulated by some receptor tyrosine kinases.
authors.affiliation: Vanderbilt Kennedy Center for Research on Human Development and Department of Pharmacology,Vanderbilt University Medical Center, Nashville, Tennessee, USA. plevitt@usc.edu
authors.forename: Pat
authors.initials: P
authors.lastname: Levitt
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Campbell