Autism spectrum disorders represent a challenge for geneticists because of the heterogeneity of causes. Still, in a subset of people with autism, certain deleterious gene mutations have been identified, and most are involved in the formation of synapses — the points of contact between neurons. At first, these mutations alone were thought to be sufficient to cause autism, but studies suggest that the inheritance of ‘modifier genes,’ which alter the expression of other genes, might contribute to the wide behavioral variability observed in individuals with autism.

Thomas Bourgeron and his colleagues at Institut Pasteur in France are aiming to obtain a detailed genomic profile of 15 families with more than one affected member (known as multiplex families). It is possible to sequence the whole genome of an individual and to identify small genetic alterations. In the nine families that Bourgeron has studied so far, deleterious mutations have been identified in NLGN4X, SHANK1, SHANK2, CNTN6 and CNTNAP2. In the six remaining families, mutations have not yet been identified, but the presence of two affected relatives with autism spectrum disorder makes it likely that an inherited genetic cause may be found.

Elucidating the gene-gene interactions at the synapses of people with autism could benefit autism research in two ways: by improving the interpretation of genetic tests for autism and by improving the design of animal models for autism. Rather than being based on the deletion of a single gene, the model animals could eventually carry multiple genetic mutations, as observed in people with the disorder.