Although autism spectrum disorders (ASD) are considered to be extremely heritable, researchers do not yet understand much about the genetic conditions that cause it. One problem facing genetics research into ASD is that autism has a highly complex genetic signature with hundreds of genes and gene variants. Researchers from Tel Aviv University, Technion-Israel Institute of Technology and Johns Hopkins University School of Medicine undertook a study to understand another piece of the puzzle. They were able to identify one of the genes in question and the role it plays in the disorder.

The research team used a novel approach to track autism’s genetic makeup. Previous studies examined the entire genome, but they were unable to identify any genes that showed up in more than one percent of people with ASD. This study, however, focused on just one gene: NHE9. This protein had been linked by other studies to autism, hyperactivity and epilepsy.

NHE9 is responsible for transporting substances from cell to cell. When there are mutations in this gene, inter-cellular communication can be inhibited. To find out what happens in the mutated NHE9 protein, the research team constructed a computer model. The model was able to predict what sorts of variants might occur in NHE9 and suggest whether the change would make a small or large impact on the cell’s communication protocols. Next, the researchers tested the mutations on a simple organism: yeast. Yeast provided a quick method for determining which mutations of NHE9 merited further study. The variations that made the cut went onto the next phase: mouse brains.

A type of cell in the mouse brains—astrocytes—was the researchers’ focal point. Astrocytes support synaptic communication by clearing away the signaling molecule glutamate once communication has finished. The researchers applied the NHE9 variants to lab-grown mouse astrocytes. They observed a change in the cell’s acidity that affected its ability to process glutamate. This increased the amount of ambient glutamate in the cell.

This mutation may have larger implications for learning and memory, but more research is needed to be sure of how and why. Additionally, increased glutamate has been shown to trigger seizures, which explains the gene’s link with epilepsy and may also account for seizures experienced by people with ASD.

The research team hopes that these findings will lead to the development of pharmaceutical treatments for autism. Once the genetic markers of autism are fully understood, it may also be possible to devise a diagnostic to identify at-risk patients.

This study is published in the journal Nature Communication.

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