TUESDAY, March 1 (HealthDay News) -- While the genetic
underpinnings of autism are enormously complex, new DNA research is
honing in on sets of abnormal genes that may play a role in the
Researchers from the Center for Biomedical Informatics at The
Children's Hospital of Philadelphia (CHOP) said that, while other
scientists have theorized about a connection between gene
mutations, impaired brain development, and the onset of autism,
their work is the first to establish the link.
The medical problem, the CHOP researchers said, has to do with
genetically driven disturbances in the way nerve cells communicate
(via synapses) as well as the manner in which these communications
are handled by key neural "messengers," or neurotransmitters.
"This large study is the first to demonstrate a statistically significant connection between genomic variants in autism and both [nerve cell] synaptic function and neurotransmission," senior author Peter S. White, a molecular geneticist and director of the Center for Biomedical Informatics, said in a hospital news release.
White and his colleagues report their findings in the March 1
online issue of
The study authors pointed out that while prior research has
implicated individual gene abnormalities with an increased risk of
autism, each particular abnormality that has been identified to
date has been linked to very small percentage of autism cases.
What's new about the current effort, the team said, is the
uncovering of entire collections of genes with similar neural roles
which, taken as a group, seem to be associated with a greater
proportion of autism risk.
The finding stems from a DNA analysis involving about 1,000
autistic children and their families, as well as parallel research
Searching for links between genetic irregularities and abnormal
motor control and/or learning disabilities, the study authors
focused on so-called CNVs -- "copy number variations" -- that occur
when the number of copies of a particular gene varies from one
individual to the next. These CNVs accounted for relatively big
chunks of the genetic mutations, the researchers said.
The gene sets of CNVs, they noted, are comprised of more DNA
structure than simple individual "snips" of DNA. These CNV gene
sets have previously been associated with a range of
neuropsychiatric disorders, such as schizophrenia, bipolar
disorder, and attention-deficit hyperactivity disorder (ADHD).
In all, about 800 CNVs were identified as exclusive to autistic
children. In addition, the CNVs in question tended to be found in
genes central to the impaired biological functions that show up in
autistic behavior, such as those involving synapse function, nerve
cell communication, and brain development, the CHOP researchers
"This suggested to us that there may be many different -- possibly even hundreds -- of genetic paths to autism, with only a few gene alterations relevant to each individual patient," White said. "But if those hundreds of genes have similar roles in the nervous system, the end result may lead to the same diagnosis: an autism spectrum disorder."
"Because the gene alterations that we found influence brain development, our hope is that they may eventually provide clues to developing diagnostic tests as well as treatments for children with autism," study co-author and CHOP child psychiatrist Dr. Josephine Elia also noted in the news release.
Ashley Scott-Van Zeeland, a postdoctoral research fellow at the
Scripps Translational Science Institute in San Diego, suggested
that the new findings may ultimately enable researchers to approach
the question of autism treatment with a broader brush.
"What this study found is that there are perhaps many autisms," she said. "There may be a number of unique or very rare genetic mutations associated with the disorder. But this suggests that they follow a common pathway that leads to autism.
"So that could mean that instead of the old paradigm of finding one mutated gene or protein and then developing a drug targeting just for that, now we could look for entire pathways involved in autism. And then potentially we could intervene with those processes with new therapeutics," she added.
For more on autism, visit the
U.S. National Institute of Neurological Disorders and