New Genetic Clues to Autism Found

2 New Gene Mutations Linked to Autism

Medically Reviewed by Laura J. Martin, MD on May 03, 2010
From the WebMD Archives

May 3, 2010 -- Researchers have discovered two new genes that may be involved with autism, the brain disorder marked by difficulty in communicating and relating to others.

The evidence for one of the two new "susceptibility genes" is stronger than that for the other, says Daniel Notterman, MD, the senior author of the study and a professor of pediatrics, biochemistry, and molecular biology at Penn State College of Medicine in Hershey.

One of the newly discovered gene mutations is in NCAM2 and the other is in PTPRD.

"We are more confident about NCAM2 and less about PTPRD," Notterman tells WebMD.

The researchers announced the discovery Sunday at the Pediatric Academic Societies annual meeting in Vancouver, British Columbia.

Autism or autism spectrum disorder, involving less severe forms of the condition, affect one in 110 U.S. children, according to estimates from the CDC.

The new finding, Notterman says, adds to the growing evidence for genetic links for autism but doesn't rule out a role for environmental factors. "Over the last couple of years, beginning in 2007, it's become clear that some cases of autism, maybe up to 15%, will be caused by rare mutations, either occurring spontaneously or that can be inherited by a parent," he says.

Tracking the Autism Genes

Notterman and his colleagues analyzed data from the Autism Genetic Resource Exchange (AGRE), a collaborative gene bank for autism, on 943 families, most of whom had more than one child diagnosed with autism. In all, they evaluated 3,742 family members.

They compared these with genetic data from 6,317 people without developmental or neuropsychiatric conditions.

Comparing genetic information on those affected with autism and those not, Notterman says, ''gave us a starting list of about 25 genetic mutations" found more commonly in those with autism.

Next, the researchers looked at whether the 25 were substantially different in the two groups, and in the process narrowed the list of suspect genes to four.

Two of the four had already been identified by researchers as linked with autism. The other two were new. "No one had shown this [link] statistically," Notterman says.

Next, Notterman's team validated the finding to see if the genes were expressed in the brain. They found that NCAM2 was ''expressed in some regions of the brain that may be associated with autism -- the hippocampus and the cerebellum."

''Many of the genes described [recently as having a link to autism] are genes involved in the synapse," Notterman says. A synapse is a specialized junction at which a nerve cell communicates with another cell.

The genetic mutation of NCAM2 is probably rare, Notterman says. "We would estimate that 0.5% or fewer of kids with autism have the NCAM2 [mutation]."

"About six to 10 rare genetic mutations to date have been associated with autism," Notterman says. "Most people working in the field predict there will be 50 to 100."

Some parents and siblings of the children with autism were found to have the NCAM2 mutation but not the disorder, which the researchers expected to find. This suggests other genetic factors or environmental triggers play a role.

Notterman conducted the research while at Princeton University. The research was supported by the Simons and Nancy Laurie Marks Foundations and the AGRE Consortium.

Tracking Autism Genes: Implications

While there is no immediate application of the discovery for parents, Notterman says the new research suggests that ''science is probably on the right track over the next decade to understand much more about the basic biology of autism.''

The recurring theme recently, he says, is the finding of structural variations in the DNA that cause mutations in the genes affecting the synapses.

Second Opinion

The new findings reflect the complexity of the origin of autism, says Daniel Coury, MD, chief of developmental and behavioral pediatrics at Nationwide Children's Hospital in Columbus, Ohio, and medical director of the Autism Treatment Network, a consortium of 14 U.S. and Canadian sites focused on improving treatment.

''There was the popular belief that we were going to find 'the gene,'" says Coury, who reviewed the study results for WebMD.

''That got expanded," he says, as ongoing research turned up several more genetic mutations associated with autism.

The recent research also suggests that genetic mutations don't seem to affect everyone equally, he says. "One of the things that was interesting," he says, "is they are seeing variations, where there are less complete [genetic] deletions in some people than in others."

Some families, he says, appear to be at greater genetic risk due to small changes in the mutations that might change how a gene is expressed. That, in turn, could affect the severity of the autism features and symptoms, he says.

While the study adds to the evidence of a genetic basis for autism, the possibility of environmental triggers is still present, Coury says. "The research is further confirmation that autism is probably caused by an interplay of genetics and environmental factors."

WebMD Health News



Daniel Notterman, MD, professor of pediatrics, biochemistry and molecular biology, Penn State College of Medicine, Hershey.

Pediatric Academic Societies Annual Meeting, Vancouver, British Columbia, Canada, May 1-4, 2010.

Daniel Coury, MD, chief of developmental and behavioral pediatrics, Nationwide Children's Hospital, Columbus, Ohio; medical director, Autism Treatment Network.

CDC: "Autism Spectrum Disorders."

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