Northport Wellness Center

July 10 (Bloomberg) -- Autism researchers plotting the intricate network of proteins and enzymes that regulate early brain development have expanded the number of gene mutations that may trigger the mysterious disorder.

Autism, which disrupts children's ability to interact socially, is linked to six new genes in a study published today in the journal Science that's the latest in a series of recent findings that have upended previous thinking about the condition. Instead of a handful of genetic mutations that might be shared by many children and explain most autism cases, researchers now believe that most cases have unique causes.

Some of the mutations found in the latest study aren't in so-called coding genes that directly control the action of proteins in the brain, the researchers said. Rather, they're in genes that help regulate other genes and exercise a more limited influence, suggesting they may offer a treatment target.

``If we can figure out how to compensate'' for these more subtle deficiencies with ``some sort of behavioral treatment or medicine,'' it may help the brain develop properly, said Eric Morrow, an instructor in psychiatry at Harvard Medical School in Boston and the lead author of the study.

``We know clinically that autism looks different in many patients,'' Morrow said in a telephone interview yesterday. So it makes sense that a disease that comes in many shapes would have multiple genetic causes, he said.

Autism affects about one in 150 U.S.-born babies, impairing their ability to communicate. It's known as a ``spectrum disorder'' because the symptoms can vary widely, causing some people to shy away from eye contact or have impaired speech while others engage in repetitive, obsessive thoughts and behavior. Some people with autism function well, while others are profoundly disabled.

The study provided intriguing evidence that autism occurs when the network of genes, proteins and enzymes that regulates early neurological development is disrupted.

``It's those processes that may have gone awry in autism and there is of course more than one way of disrupting a pathway,'' said Michael Greenberg, the director of the neurobiology program at Children's Hospital in Boston.

Greenberg has been studying the way that synapses, the junctions between neurons where chemical signals pass back and forth, mature in the brains of young children in response to their experiences. He and his colleagues have mapped the pathways that are followed as neurons receive messages, triggering complex reactions that turn genes on and off.

Greenberg's team has found at least 300 genes that are activated in this process and communicate with the cell, telling it to make a new synapse or strengthen or destroy an existing one. Three of these genes were among the six found by a second team to trigger autism in the group of 88 children and their parents whose genes were analyzed for this study.

Scientists suspect the flaws are contained in some genes inherited from parents while others arise spontaneously. The second team studied autistic children and their parents from eight Middle Eastern countries -- Jordan, Saudi Arabia, Kuwait, Oman, Qatar, the United Arab Emirates, Pakistan and Turkey.

Because the parents of each child are cousins, researchers could assess the role played by recessive genes carried by each parent. By comparing the gene maps of each autistic child and their parents, they could look for shared segments of DNA that are the same.

``Our hypothesis is that the disease can be carried by inheriting a mutation that both mother and father carry,'' Morrow said. ``Parents have each inherited one copy from their common ancestor, and the child will get two copies.''

They found what they were looking for in a handful of the cases, Morrow said. In those cases, the team found that within chromosomal regions inherited from both parents, there were large sections of the chromosome that was deleted.

``The children had a segment of DNA that's gone,'' he said.

One discouraging aspect of recent findings in autism is the growing sense that a disease caused by a large number of genetic mutations that differ from one child to the next will be challenging to treat.

The hopeful part of the new work, Morrow said, is the team's finding that many of the genes implicated in autism appear to perform similar functions in organizing the structure of the developing brain. Even more positive is the suggestion that some of the deletions and flaws are in regulating rather than coding genes. That may mean that scientists can find ways to turn target genes on or off to compensate for the mutation.

Studies have shown that when autistic children are placed in enriched learning environments, some make significant progress. That suggests the children are getting the experiences they need to activate the genetic pathways that help organize the brain's developing structure.

``As progress is made in understanding the proteins involved in autism and knowing how they function in the network, we may find that if you tweak the pathway in one way or another, you might be able to have a therapy,'' Greenberg said.

New Genes, Ideas on Autism Emerge in Families' Study (Update1)