A New Genetic Mechanism for Autism

It has been almost half a century since Leo Kanner first described the clinical phenotype associated with Autism1. Since Kanner's descriptions, much effort has been devoted to understanding and identifying the factors which may contribute to Autism. It was not until the early 80’s that compelling evidence started to accumulate suggesting that Autism is a disorder of abnormal brain development. It is now generally accepted that both genetic and environmental factors are implicated in the etiology of this intriguing condition. In the current chapter, we will focus on the role of genetic factors involved in the pathogenesis of Autism. While multiple hypotheses have been proposed to account for the genetic origin of Autism, some have received more empirical support than others. While it is likely that more than one genetic mechanisms is involved in the pathogenesis of this disorder, this chapter will focus on a recent hypothesis implicating de novo mutations in synaptic genes. This hypothesis is based on the proposition that rare, highly penetrant mutations affecting any of many different genes which code for synaptic molecules, and which are specific to single families, predispose to Autism. Empirical lines of evidence for this hypothesis will be presented, along with examples, some of which are derived from work by our group.