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HEALTH & SCIENCE

Study advances insight into autism's genetic hot spots

Findings support the multifactorial nature of this neurodevelopmental disorder and give hope for the discovery of biological targets for therapies; vaccine link still questioned.

By Stephanie Stapleton, AMNews staff. Sept. 17, 2001. Additional information


Washington -- Science is one step closer to unlocking the genetic basis of autism -- the puzzling neurodevelopmental disorder that effects, in some form, at least one in 500 people.

Researchers have identified the regions of four chromosomes that appear to be linked with the disorder, according to a study supported by the National Institutes of Health and published in this month's American Journal of Human Genetics.

"These findings confirm the role of genetics in autism and are a major step in narrowing the search for the specific genes involved," said Duane Alexander, MD, director of NIH's National Institute of Child Health and Human Development and co-chair of NIH's Autism Coordinating Committee.

The idea that there is an inherited component to autism is not new. Earlier studies have offered varying degrees of evidence. This study is important because it "is another link in this chain," said Marie Bristol-Power, PhD, the NICHD special assistant for autism. "This paper replicates findings on two of the genetic hot spots."

Specifically, the researchers screened the DNA of more than 150 pairs of siblings with autism -- all of whom were diagnosed using the same methods. The study, involving subjects and researchers from seven countries, was carried out by members of the International Molecular Genetic Study of Autism Consortium.

They found evidence that two regions on chromosomes 2 and 7 contain genes involved in the disorder.

"The chromosomes they are on make sense in terms of autism," said Dr. Bristol-Power. Chromosome 7 is known to be associated with many language disorders and has been shown to be linked with autism in some earlier studies, but not all.

Researchers were particularly excited by evidence of an autism link on chromosome 2, since this area had recently been identified by another, independent research group. Likely locations for autism-related genes were also found on chromosomes 16 and 17, although this correlation was weaker, according to the NICHD.

Overall, the study is important because it adds support to the concept that autism is caused by more than just a single gene -- that it is multifactorial, the result of interactions between several genes involved in brain signaling and development, as well as environmental factors.

"It's likely we're talking about a genetic susceptibility rather than a genetic cause," explained Dr. Bristol-Power. And it then leads to questions about what else might contribute.

NICHD is supporting a range of research looking at the interaction between the genes for early brain development located on chromosome 2 and environmental influences.

In the long run, chromosome 7's role is interesting, too, because this chromosome has been linked with other language disorders.

"What we are trying to find are biological markers and biomedical treatments for autism," Dr. Bristol-Power said.

If this plays out, it would allow for earlier diagnosis and earlier interventions. For instance, if a gene for language could be identified, there would be a biological target for therapies that could at least help with the development of language skills.

Vaccine study: Largest to date

Meanwhile, findings in a separate study, published in the Aug. 30 New England Journal of Medicine, address concerns about the possible link between two widely used vaccines and the onset of autism and other neurodevelopmental problems.

This study was conducted because the risk of seizures and such subsequent disorders has not been clearly identified in children vaccinated with DTP (for diphtheria-tetanus-pertussis) and MMR (for measles-mumps-rubella), according to the Journal's weekly briefing materials.

These questions about risk provide context to some parents' fears that they might be hurting their children by having them immunized. Others point to vaccination schedules as a possible factor in their child's illness.

Centers for Disease Control and Prevention researchers concluded that the two vaccines were associated with a short-term increased risk of fever-related seizures, but that these seizures were not associated with an increased risk of subsequent seizures or neurodevelopmental disabilities. This lack of association is reassuring, according to the authors.

Using records from the Vaccine Safety Datalink project -- a study begun in 1991 to look at adverse events after childhood immunization, the researchers examined the medical data of more than 600,000 children younger than seven years. The children who were followed received vaccines between 1991 and 1993. In the time since, that form of DTP vaccine has been replaced with a new form called DTaP.

The study first sought to pinpoint children who had had seizures. From this group, researchers gathered specific information about these seizures -- if they were fever- or nonfever-related events and whether they were attributable to trauma or an existing disease, such as epilepsy.

The researchers then analyzed the risk of a first seizure after DTP or MMR vaccination. Children who had post-vaccination febrile seizures were followed to identify the risk of subsequent seizures and other neurological problems, including learning disorders, mental retardation and infantile autism, according to the article.

Barbara Loe Fisher, co-founder and president of the National Vaccine Information Center, takes exception with both the study and its findings, saying the conclusions are "irresponsible and dangerous" and that the methodology is flawed.

She is disheartened by what she considers to be the study's message: "If your child has a seizure after vaccination, it doesn't matter. Keep vaccinating them. Our message has always been that there are some children who cannot tolerate vaccines," she said.

The NVIC calls for longitudinal studies comparing health outcomes, morbidities and mortalities of children who have been vaccinated and those who have not. It also supports efforts to identify biomarkers to screen children and determine who is at risk.

But NICHD's Dr. Bristol-Power said, for now, the clues that genetics is providing are not directly related to questions about a link between vaccines and autism. And the size of the New England Journal study and its findings seem to suggest that, for most children, the role of vaccines will unlikely offer a simple answer to the "in the presence of what" question associated with the triggers of autism, she added.

ALL INFORMATION, DATA, AND MATERIAL CONTAINED, PRESENTED, OR PROVIDED HERE IS FOR GENERAL INFORMATION PURPOSES ONLY AND IS NOT TO BE CONSTRUED AS REFLECTING THE KNOWLEDGE OR OPINIONS OF THE PUBLISHER, AND IS NOT TO BE CONSTRUED OR INTENDED AS PROVIDING MEDICAL OR LEGAL ADVICE.  THE DECISION WHETHER OR NOT TO VACCINATE IS AN IMPORTANT AND COMPLEX ISSUE AND SHOULD BE MADE BY YOU, AND YOU ALONE, IN CONSULTATION WITH YOUR HEALTH CARE PROVIDER.