Gene discoveries may help explain how autism works

Study shows brain can't properly set new connections

WASHINGTON - Harvard researchers have discovered a half-dozen genes involved in autism that suggest the disorder strikes in a brain that can't properly form new connections.

The findings also may help explain why intense education programs help some autistic children - because certain genes that respond to experience weren't missing; they were just stuck in the "off" position.

"The circuits are there but you have to give it an extra push," said Dr. Gary Goldstein of the Kennedy Krieger Institute in Baltimore, which wasn't involved in the gene hunt but is well known for its autism behavioral therapy.

The genetics suggest that "what we're doing makes sense when we work with these little kids - and work and work and work - and suddenly get through," he said.

But the study's bigger message is that autism is too strikingly individual to envision an easy gene test for it. Instead, patients are turning out to have a wide variety of gene defects.

"Almost every kid with autism has their own particular cause of it," said Dr. Christopher Walsh, chief of genetics at Children's Hospital Boston, who led the research published in today's edition of the journal Science.

Autism spectrum disorders include a range of poorly understood brain conditions, from the mild Asperger's syndrome to more severe autism characterized by poor social interaction, impaired communication, and repetitious behaviors.

It is clear from studies of twins and families with multiple affected children that genes play a big role in autism. But so far, the genetic cause is known for only about 15 percent of autism cases, Walsh said.

So Walsh's team employed a different strategy. It turned to the Middle East, a part of the world with large families and where cousins marry, characteristics that increase the odds of finding rare genes. They recruited 88 families with cousin marriages and a high incidence of autism from Jordan, Saudi Arabia, Kuwait, Oman, Pakistan, Qatar, Turkey, and United Arab Emirates. They compared the DNA of family members to search for recessive mutations - where mother and father can be healthy carriers of a gene defect but a child who inherits that defect from both parents gets sick.

In some of the families, they found large chunks of missing DNA regions that followed that recessive rule. The missing regions varied among families, but they affected at least six genes that play a role in autism.

Here's why this matters: All the genes seem to be part of a network involved in a basic foundation of learning - how neurons respond to new experiences by forming connections between each other, called synapses.

In the first year or two of life - when autism symptoms appear - synapses rapidly form and mature, and unnecessary ones are "pruned" back. In other words, a baby's brain is literally being shaped by its first experiences so that it is structurally able to perform learning and other functions of later life.

"This paper points to problems specifically in the way that experience sculpts the developing brain," explained Dr. Thomas Insel, director of the National Institute of Mental Health, which helped fund the work.