Autism, the best known of the autism spectrum disorders (ASDs), is a relatively common condition affecting around 1 in 150 children in the US, with about four times more boys than girls affected. People with autism spectrum disorders struggle with social communication and interactions, and have difficulty relating to other people and their emotions. A number of factors – both genetic and environmental – have been suggested to be linked to autism and two recent studies have now provided evidence of associations with genetic variations.
In the first study, which is published in the journal Nature, variations in a region close to the genes for two neuronal cell-adhesion molecules, cadherin 9 (CDH9) and cadherin 10 (CDH10) were found to occur more frequently in children with ASDs than in unaffected children. These cadherin molecules, which are expressed on the surface of neurons, mediate calcium-dependent cell-cell adhesion and are important in shaping the physical structure of the developing brain as well as the functional connections between different areas of the brain. The researchers propose that these gene variants are new susceptibility factors for ASDs and estimate that they may contribute to up to 15% of cases.
The second study, also published in the journal Nature, identified copy number variations – deletions or duplications of DNA – in genes belonging to two biological pathways. Interestly, one pathway involved the same neuronal cell-adhesion molecule gene family that was identified in the first study, whilst the other involved genes in the ubiquitin degradation pathway. The role of ubiquitin, which tags proteins – including the neuronal cell-adhesion molecules – for proteasome-mediated degradation, presents a mechanism that links the two gene pathways. The new data support previous evidence from functional magnetic resonance imaging studies showing that children with ASDs may have reduced connectivity among neural cells, and with anatomy studies that have found abnormal development in the frontal lobes in autistic patients.
Although the new information does not fully explain why some children develop ASDs and cannot immediately be used to provide clinical treatments, it should provide ideas for further experiments that may eventually lead to strategies for the prevention or early treatment of ASDs.