A newly identified gene that is associated with severe autism provides new clues about the factors that cause this neurodevelopmental disorder. The gene, described in this week's Nature, has a role in neuronal development. Some defects in this gene lead to impaired development and maintenance of neural circuits in the brain, which may impact cognitive function, and seem to contribute to rare severe cases of autism in females.
Autism affects four times as many males as females; consequently, it is hypothesised that females are affected only by severe variations to autism genes that affect key developmental processes. To identify such candidate genes, Tychele Turner, Aravinda Chakravarti and colleagues analysed protein-coding genes in 13 females with severe autism. Despite the small sample size, the authors identify 18 candidate genes that have potentially harmful variants, including a gene called CTNND2, which encodes a protein called delta-2 catenin. Experiments in zebrafish, a model organism for studying human disease, demonstrate that loss of function of this gene has deleterious effects for the development and/or maintenance of synapses. These findings highlight a critical role for the CTNND2 gene in neuronal development and in autism.