U. researchers discover another genetic link to autism

New study » Mutations near chromosome 5 may increase susceptibility
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An international consortium of researchers, including three from the University of Utah, has discovered yet another genetic link to autism.

Studying the genes of more than 1,000 families -- including 150 from Utah -- who have more than one person with the disorder, the researchers found a region on chromosome 5 that is strongly associated with autism, according to a study published Thursday in the journal Nature .

Not just one, but multiple rare mutations were found near a gene called semaphorin 5A (SEMA5A). It plays a role in the creation of a protein that is involved in the development of neurons.

What's more, the researchers found, the mutations were likely to be different from one person to the next.

While autism is recognized as a hereditary disorder, previous attempts to find the genes that increase susceptibility have only been marginally successful.

"Anytime a gene is implicated in a really large sample like this, it's of more interest because we have more confidence that it's real," said Hilary Coon, a U. professor of research and a co-author of the study.

Identifying the gene by itself, however, doesn't tell researchers how to develop treatments or "even how it plays out in one individual to the next."

Coon stressed that autism is a complex disorder that involves hundreds of other genes that have already been implicated.

"It's just becoming clear the puzzle has way more pieces than anyone thought," she said.

Autism, according to the National Institutes of Health, is a disorder characterized by difficulty with communication, social impairments, and restricted, repetitive and stereotyped patterns of behavior.

A study also published this week in the journal Pediatrics revealed that as many as one in 91 children have the neurodevelopmental disorder, up from previous estimates of 1 in 150. Coon largely attributes the difference to heightened awareness of autism, as well as a broadening of its definition to encompass a broad spectrum of disorders.

For the SEMA5A study, researchers first studied 1,031 families, with a total of 1,553 children affected by autism, from the Autism Genetic Resource Exchange and U.S. National Institutes of Mental Health repositories.

To confirm their findings, they replicated the study using data from the Autism Consortium, Autism Genome Project, and other autism family samples from around the world and Utah. They also compared brain bank tissue from 20 persons with autism to tissue from those who do not have the disorder, and found that expression of the SEMA5A gene was significantly lower in the brains of those with autism.

Robert Payne, waiting at Autism Journeys in Lehi while his son, Harrison, attended a session, said the study was good news.

"I'm glad to hear something's being done to know what causes this," the Riverton resident said.

He said the research may convince insurance companies that autism disorders are medical conditions and deserve full coverage. Too often, he said, it is dismissed as a behavioral problem, something Payne admits to doing before he had a child with autism.

In the 2009 session of the Utah Legislature, Draper Republican Sen. Howard Stephenson sponsored "Clay's Law," which would have mandated insurance coverage for autism. The legislation died when the House of Representatives failed to vote on it before the session ended.

Payne said insurance coverage would make it easier to get children into therapy earlier and help them to lead productive lives.

He said Harrison, who was first examined for autism at 3 and started therapy earlier this year at age 5, has made significant progress -- he can now stand in line and sit through an hour-long church service, things that had been almost impossible.

But without insurance, Payne said he will likely burn through the family's savings in two years just to pay for therapy.

For Kate Andersen, president and founder of Lehi-based Autism Journeys, the study wasn't too surprising. Her center treats families where multiple members -- including a parent and children -- have autism-spectrum disorders.

But she said there are also many people who believe genetics has nothing to do with autism. Andersen said she doesn't get involved with the debate.

"The cause of autism is not going to change treatment," Andersen said. "It may help with family counseling."

She said the research is also helpful in keeping autism disorders in the forefront of both research and public awareness.

William M. McMahon, professor and chairman of psychiatry at the U.'s School of Medicine and Judith S. Miller, an associate professor of psychiatry, were a contributor and co-author of the study.

Tribune reporter Lisa Schencker contributed to this report.


What's next?

Hilary Coon, a University of Utah professor of research, said the next step is to study how these genetic elements segregate between family members; and whether they occur in people who are not clinically affected, but may have some characteristics of autism.

Researchers are also interested in studying the life course of an autistic patient and determining if and how these mutations may play out in adulthood, she said.

A complex puzzle

Hundreds of genes have been implicated in autism. A change on chromosome 15, for instance, can explain between 1 to 3 percent of autism cases.

While the new discovery involving chromosone 5 does not immediately reveal a direction for developing treatments, it is another step toward understanding the complex disorder, researchers said.