French researchers have combined three clinical, neurophysiological and genetic approaches to better understand the brain mechanisms that cause autism.
Researchers at Inserm and Tours Regional University Hospital used the approach with two families to help them identify specific gene combinations in autistic patients that distinguished them from patients with intellectual disabilities.
Investigators believe the approach offers new prospects for the diagnosis and understanding of the physiological mechanisms of autism.
The study appears in the journal Molecular Psychiatry.
Autism is a condition characterized by great heterogeneity, both in terms of clinical manifestations and genetics. It is currently estimated that nearly 400 genes may be involved in this disorder.
Diagnosis of this condition is all the more complex because it is often associated with other developmental disorders involving the same genes.
To improve diagnosis, the Inserm researchers used an original multimodal approach combining:
- clinical assessment;
- high-throughput genomic analysis to sequence all the genes;
- analyses of the electrical activity of the brain in response to the perception of a change (electroencephalography (EEG)).
Two families with members affected by autism and/or intellectual disability were given the benefit of this integrated approach.
In these two families, all individuals affected by the condition carried a mutation in the NLGN4X gene, which manifested in the brain as problems in transmitting information by the neurons.
Using EEG, the researchers primarily observed an abnormal brain wave pattern, characteristic of patients with autism. The other family members, including those with intellectual disabilities, did not show this feature.
Thanks to this new approach, a second rare mutation was characterized and linked to atypical brain activity measured by EEG in autistic patients.
According to researchers Drs. Frédéric Laumonnier and Frédérique Bonnet-Brilhault, “This study helps us realize that there is no ‘gene for autism,’ but combinations of genes involved in neurodevelopment that affect the development of the neuronal networks targeted by this condition.”
Investigators believe that identifying these combinations is a key step in understanding the physiopathology, and ultimately in the development of targeted therapeutic drugs.