A new study published in PLoS Genetics uses a combination of genetic and neurobiological approaches to confirm that synaptic mutations increase the risk of autism spectrum disorders (ASDs) and underlines the effect for modifier genes in these disorders.

ASDs, a heterogeneous group of neurodevelopmental disorders that have a complex inheritance pattern, appears before the age of three years and affects 1 in 100 children, with a higher risk for males than females. The disorder is characterized by impairments in social interaction and communication as well as by restricted and repetitive behavior. Scientists have identified several genes involved in ASD in those who have been diagnosed. However, understanding of their effects on neuronal functions and their interaction with other genetic variations has only recently been learnt.

In their new multi-center international study, Leblond and his collaborators detected mutations altering SHANK2, a gene that encodes a scaffolding protein located at synapses (contacts between neuronal cells). The researchers demonstrated that several of the observed mutations in patients decreased the number of synapses in neuronal cell cultures and a further genomic analysis of three patients with SHANK2 deletions revealed additional rare genomic imbalances that were previously linked to other neuropsychiatric disorders, which could act as modifier genes by modulating the disorder.

These findings highlight the significance of synaptic gene dysfunction in ASD and also underline the role for modifier genes, affirming a "multiple hit model" for ASD. Thomas Bourgeron, one of the study authors, concludes:

"A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD."

Written by Petra Rattue