Advances in autism genetics: on the threshold of a new neurobiology

Abstract

Autism is a he terogeneous syndrome that is defined by impairments in three core domains — social interaction, language and restricted and/or repetitive behaviour. Defined mutations, genetic syndromes and de novo copy number variation probably account for about 10–20% of autism spectrum disorder (ASD) cases, with none of these known causes accounting for more than 1–2%. None of the molecules or syndromes currently linked to the ASDs has been proven to selectively cause autism. Instead, each seems to result in an array of abnormal neurobehavioural phenotypes, including ASDs and non-syndromic mental retardation. Understanding why these mutations lead to ASDs in only a subset of cases — through identification of genetic and/or environmental modifiers — will help to clarify how the specific aspects of cognition and behaviour are ultimately shaped. The identification of molecular links between distinct ASD-related syndromes will lead towards the identification of key signalling pathways that are dysregulated in the ASDs.