New research has singled out a genetic hotspot related to autism spectrum disorders: a gene identified as TRIO, which influences the development and strength — or weakness — of the connections between brain cells.

The scientists found eight autism-associated mutations clustered within a small region of the Trio protein. Changes in the protein’s function early in a child’s brain development can, like a line of dominoes, set off a chain reaction that hampers connections between brain cells, and consequently, hinder the brain’s ability to store and process information.

“I have never seen this number of autism-related mutations in such a small area,” said Bruce Herring, the study’s corresponding author and a neurobiologist at the USC Dornsife College of Letters, Arts and Sciences. “The likelihood that this number of mutations occurs by chance is 1 in 1.8 trillion. We’re pretty confident these mutations contribute to the development of autism-related disorders.”

Herring’s laboratory at USC Dornsife studies the molecular mechanisms underlying neuroplasticity, and this includes the strengthening or weakening of synaptic connections between cells that influence the brain’s ability to store and process information. For this study, Herring and his team studied the genomes of 4,890 people with autism-related disorders, looking for genetic patterns.

“TRIO ended up very high on our list,” Herring said.

The team found eight mutations associated with autism in a small area of the TRIO gene — the GEF1/DH1 domain. This domain encodes a specific area of the Trio protein that turns on another protein, Rac1, which causes the growth of actin filaments — think of them as the scaffolding that underpins brain growth.

Most of the autism-related mutations discovered in this study prevent the Trio protein’s ability to activate Rac1. The interference causes the scaffolds to break down, weakening the brain’s connections. As a result, the brain cells have trouble communicating with each other.

Previous studies have identified a variety of types of problems with brain cell connections that are linked to autism. In some cases, the connections between brain cells appear weaker than normal. In other cases, they seem too strong. While most of the eight TRIO gene mutations weaken the Trio protein, causing weaker connections between brain cells, the researchers did find one that caused the Trio protein to become much stronger and cause too many neural links. Since autism is a spectrum, or range, of conditions, it’s possible that too much and not enough Trio could be causes of autism disorders.

“The ability of our brains to increase and decrease the strength of connections between brain cells is essential for normal brain development; our brains must be plastic,” Herring said. “Mutations that push connections too far in either direction are likely to impede our brain’s ability to change in appropriate ways. We believe autism-spectrum disorders are likely to develop from mutations that take away the brain’s ability to change during a critical time point in a child’s brain development, when the brain cells are trying to establish the appropriate connections and build the right circuits.”

The findings were published in the journal Nature Communications.