Chromosome Abnormality Linked to Autism

January 9, 2008

by Catherine Arnst

Scientists have discovered the strongest link yet between specific chromosomal abnormalities and an increased risk of autism, the neurological disorder that affects up to one in every 166 children in the U.S.

The abnormalities were linked with certainty to only 1% of autism cases. But the researchers, reporting in the latest issue of the New England Journal of Medicine, say their work points the way to finding other genetic changes linked to the disease, as well as potential treatments—and prenatal screening tests that could spark ethical questions.

Using a very large genome scan, the researchers also discovered that the genetic abnormalities—either a deletion or a duplication of a section of chromosome 16—were not directly inherited from either parent. Instead they developed spontaneously during the embryonic stage of development, possibly due to interplay of various genetic factors inherited from the parents.

Through the use of new and very costly chromosome micro-array tests, doctors can detect the abnormalities in autism patients and their parents and then predict the risk of recurrence in subsequent pregnancies. "We are beginning to develop a full understanding of the autism spectrum disorder genome which…ultimately will lead to the discovery of treatments that have the greatest promise," says Eric Lander, director of the Broad Institute of MIT and Harvard, which took part in the research.

The discovery marks another win for deCODE Genetics of Iceland, which also conducted some of the research. The company has used its population screening technology, and its extensive database of Icelanders' genomes, to locate the genetic links to a huge range of diseases.

Autism spectrum disorder, as it is formally known, is a profound developmental disease that affects speech, behavior, and cognition. Doctors know the disease runs in families—90% of cases may be genetic—but the genetic pathways have been extremely difficult to identify, likely because more than one is the culprit. Only in 10% of cases can it be linked to specific and well-known genetic anomalies, such as fragile-X syndrome.

Many parents long feared thimerosal, a preservative once contained in many childhood vaccines, was the culprit, but study after study has failed to find any link. Most recently, an extensive federal study (BusinessWeek.com, 1/7/08) released Jan. 7 found autism rates in California have continued to rise over the last several years, long after thimerosal was removed from almost all vaccines in 2001.

The New England Journal study was conducted by a team put together by the non-profit Autism Consortium. The other participants were Children's Hospital in Boston and Massachusetts General Hospital. The consortium initially screened the genomes of more than 3,000 people, including 1,441 diagnosed with autism, and found a deletion of the same section of chromosome 16 in five of the autism patients. Children's Hospital scientists found five more cases of that genetic deletion in testing of 512 people suspected of having autism, and deCODE found the same in 3 out of 299 autism patients. The researchers also discovered 11 patients had extra copies of genes in the same region of chromosome 16 where others were missing genes.

Other researchers have identified chromosome 16 anomalies in patients with autism, but this study is by far the largest genome scan for the disease to date. The region of chromosome 16 missing or duplicated contains some 25 genes whose functions are not known. David Miller of Children's Hospital, a co-author of the New England Journal paper, says his team plans further study of the region to identify exactly which of these genes is most closely linked to autism.

"The immediate benefit, though, will be to help us clarify the diagnosis when a determination of autism is difficult to make," says Miller. He cautions, however, that any prenatal test, such as the one that screens for Down's syndrome, is years away, as more precise knowledge of the genetic causes of autism is needed. Some parents of autistic children have already been vocal in their opposition to routine prenatal screening for autism, should such a test come about, because it may lead prospective parents to abort fetuses that, as children, could have been treated successfully, or might never have developed the disease at all.

Arnst is a senior writer for BusinessWeek based in New York .

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