Diverse Autism Mutations May Share Common Mechanism

Many of the seemingly diverse mutations that lead to autism may cause the disorder through a similar underlying mechanism, according to a new study.

In recent years, researchers have linked several rare mutations with autism. Collectively, they account for at least 10% of sporadic, non-inherited cases of autism. Inherited genetic factors have also been tied to autism. A research team led by Dr. Christopher Walsh and Dr. Eric Morrow of Harvard University set out to look for such factors. Their work was supported by NIH’s National Institute of Mental Health (NIMH), along with several other NIH components.

The scientists searched for genes and mutations associated with autism in 88 families from the Middle East, Turkey and Pakistan in which cousins married and had children with autism. They studied families in which parents share ancestry because the strategy increases the chance of finding inherited genetic factors that contribute to autism.

The researchers reported in the July 11, 2008, issue of Science that they linked several gene mutations to autism. The largest group of implicated genes is regulated by neuronal activity. These genes are involved in the changes in synapses—the areas between neurons in the brain—that underlie learning.  Whether they turn on is dependent on experiences that trigger neuron activity. Such genes are vital to the developing brain.

“The one unifying observation from this new report is that all of the relevant mutations could disrupt the formation of vital neural connections during a critical period when experience is shaping the developing brain,” NIMH Director Dr. Thomas R. Insel explained.

Numerous mutations may be linked to autism, but this study suggests that common mechanisms may underlie the reasons they all lead to the disorder. “Autism symptoms emerge at an age when the developing brain is refining the connections between neurons in response to a child's experience,” Walsh explained. A common mechanism of autism-associated mutations may be that they lead this delicate refinement process to go awry.