November 27, 2000

Researchers Identify Gene Common to Many Autism Cases

Researchers funded by the National Institutes of Health have identified a gene that may predispose people to developing autism. The gene, known as HOXA1, plays a crucial role in early brain development. The study was conducted by a research team in NIH's Collaborative Programs of Excellence in Autism and was published in the December issue of Teratology.

"These findings strongly suggest that a gene controlling early brain formation may underlie the development of autism in a large number of cases," said Duane Alexander, M.D., Director of the National Institute of Child Health and Human Development (NICHD) and chair of NIH's autism coordinating committee.

The spectrum of disorders known collectively as autism frequently involve problems in communicating with others and difficulty interacting socially. Many people with autism exhibit repetitious hand and body movements. Roughly one in 500 persons may be affected by some form of the disorder. The research team was led by Jennifer Ingram, Ph.D., and Christopher Stodgell, Ph.D., of the University of Rochester School of Medicine and Dentistry in Rochester, New York. The research was conducted as part of the NIH Collaborative Program of Excellence in Autism (CPEA). This $42 million research initiative is an international network of ten research teams seeking to unravel the mysteries of autism. The network is co-funded by the NICHD, the National Institute of Deafness and Other Communication Disorders, and the National Center for Complementary and Alternative Medicine.

The researchers tested 57 people diagnosed with autism for a variant of the HOXA1 gene. Of these, 22--about 40 percent-had one copy of the variant. Only one person with autism carried two copies of the variant gene, said the study's senior investigator, Patricia M.Rodier, Ph.D., of the University of Rochester School of Medicine. When the researchers tested hundreds of people without autism, they found that people who had two copies of the variant were even less common. This suggests that having two copies of the mutant gene interferes with survival.

Moreover, after testing the genes of parents and other family members of people with autism, the researchers found that symptoms of autism were more common in people who inherited the variant gene from their mothers than in those who inherited the same gene from their fathers. Dr. Rodier said that this agrees with several other studies of patterns of autism in families; inheritance from the mother seems to play a strong role in who develops the disorder.

Dr. Rodier and her coworkers first thought to investigate the HOXA1 gene after reviewing the pattern of birth defects resulting from prenatal exposure to thalidomide. Children born to mothers who took the drug during pregnancy have sometimes been born with autism. Some of the autistic children born to mothers who took thalidomide also had misshapen ears, as well as abnormalities in the nerves of the head and face.

Previous studies of these children suggest that the damage to the ears and facial nerves resulted between the 20th and the 24th days after conception. This time span marks the development of brain regions that later control the muscles of the eyes, face, tongue, jaw, and throat. Because mice engineered to lack the HOXA1 gene show similar patterns of brain and ear abnormalities, the researchers tested autism patients for abnormalities of the corresponding human gene.

"One by one, we're finding the genes responsible for the autism spectrum disorders," said Marie Bristol-Power, Ph.D, NICHD special assistant for autism programs. She noted that other NICHD-funded investigators previously have discovered genes for two autism-related disorders, Rett syndrome and Fragile X syndrome.

As is the case with such findings, the Rodier group's report must be confirmed by other researchers. The other teams in the CPEA will seek to reproduce the findings in the near future.

Additional information about autism is available on the NICHD autism page, http://www.nichd.nih.gov/autism/.

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