03/05/2010

Researchers discover two new genes which may be involved in autism

VANCOUVER, Canada: Researchers have discovered two new genes that may be involved in autism. The evidence for one of the two new "susceptibility genes" is stronger than that for the other, says Dr Daniel Notterman, the senior author of the study and a professor of paediatrics, 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," Dr Notterman told WebMD.

The researchers announced the discovery on May 2 at the Pediatric Academic Societies annual meeting in Vancouver, British Columbia.

The new finding, Dr Notterman says, adds to the growing evidence for genetic links for autism but does not rule out a role for environmental factors. "Over the plast 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.

Dr Notterman and his colleagues analysed 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, Dr 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," Dr Notterman says.

Next, Dr 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," Dr Notterman says. A synapse is a specialised junction at which a nerve cell communicates with another cell.

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

"About six to 10 rare genetic mutations to date have been associated with autism," Dr Notterman adds. "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.

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

(Source:  WebMD, May 3, 2010)

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