Gene mutations, autism linked

Putting the pieces of the complex puzzle of autism together bit by genetic bit, scientists at Cold Spring Harbor Laboratory in New York have identified dozens of spontaneous mutations that lead to a common pathway to the brain disorder.

Until recently, scientists have been looking for several specific genes that run in families, which could help explain why some children are born with autism. Last month, the Centers for Disease Control and Prevention announced that 1 in 150 children are born with autism.

In this new study, published Friday in Science, Jonathan Sebat, Michael Wigler and their colleagues found that 10 percent of the 195 autistic patients they studied had evidence of tiny spontaneous chromosomal mutations — each with a different gene involved. Ultimately, Sebat said he believes this could help some parents who are seeking to have more children but fearful that they will take another genetic hit with their next child.

A spontaneous mutation means it is not inherited.

According to Sebat, an associate professor of genetics at the Long Island research lab, technology until now could not provide enough resolution to see many of these small chromosomal abnormalities.

Humans have 23 pairs of chromosomes, which include a pair of sex chromosomes. People differ substantially in the chromosomal structure and can have repeats or deletions in stretches of the DNA, according to earlier work by the same team.

Scientists are not sure why.

"In autism, there are a certain number of individuals who have more variation in the number of copies of genes," said Pat Levitt, director of the Vanderbilt Kennedy Center in Tennessee and an expert on autism who is not involved in the study. "This is an important finding."

In blood samples from the autistic patients and an equal number of unaffected siblings and parents, 10 percent of them had spontaneous genetic mutations compared with 1 percent of those in a control group. In families with more than one autistic child, there were very few of these spontaneous chromosomal rearrangements. It's akin to a reshuffling of the chromosomes.

But what was most surprising is that all of the mutations appeared at different places along the genome, suggesting, as Sebat said, "that there are so many possible places where you can get a hit."

The end result of these genetic mutations is that these children have impaired social interactions, difficulty communicating, restricted interests and language deficits.

"The brain has a particular way of responding to many different types of cognitive impairment," Sebat said.