June 9, 2010 -- Accumulation of rare DNA mutations in genes affecting brain function appears to be a major cause of autism, a large international study suggests.

"This will lead to a paradigm shift in understanding causes of autism," study researcher Stephen Scherer, PHD, of Toronto's Hospital for Sick Children, said at a news conference held to announce the findings.

Finding the cause of autism is like trying to put together a huge jigsaw puzzle with no idea of what the final picture should look like, says study researcher Anthony Monaco, MD, PhD, of the U.K.'s University of Oxford.

"What we have found are the edges of the puzzle. We now can say some of the pieces are the sky or the sand of the picture," Monaco said at the news conference. "We now see that some of the genetic changes in autism are related to connections in the brain."

The study used recently developed technology to look for unusual DNA deletions or duplications -- known as copy number variants or CNVs -- in 996 people with autism and 1,287 matched people without autism.

People with autism didn't have more CNVs than people without autism, and their CNVs weren't any bigger than usual. But in autism, CNVs are much more likely to occur in gene-containing regions of the genome.

And many of the genes in which these rare CNVs occur are linked to brain function -- especially the growth and maintenance of the synapses through which brain cells communicate with each other.

"This basically shows us that CNVs can account for a pretty appreciable percentage of autism spectrum disorder," study researcher John R. Gilbert, PhD, of the University of Miami's Institute for Human Genetics, tells WebMD.

The CNVs implicated in autism aren't all the same. In fact, the most common CNV identified in the study occurred in less than 1% of people with autism. Nearly every child studied has a unique CNV profile.

But in people with autism, CNVs cluster around networks of gene sets -- pathways -- that control brain-cell development and function. That's the paper's most important finding, says study researcher Louise Gallagher, MD, PhD, of Trinity College Dublin.

"So even if children have different genes that are influencing the development of their autism, we hope that if drug companies or biotech companies target these pathways, that the therapies might work for a broad number of the children who are affected," Gallagher said at a news conference. "Some of these therapies would still work because they act on pathways that are linked."