New Genetic Clues to Autism Found
2 New Gene Mutations Linked to Autism
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
"We are more confident about NCAM2 and less about PTPRD," Notterman tells
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
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,"
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
''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