Researchers Identify Gene Linked to Autism

November 27, 2000

In a medical first, researchers at the University of Rochester Medical Center have identified a gene that may predispose people to developing autism. The gene, known as HOXA1, plays a crucial role in early brain development and is the first gene linked to autism. The study is being published in the December issue of the journal 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, part of the National Institutes of Health.

Autism and several related disorders frequently involve problems in communicating with others and difficulty interacting socially. Many people with autism are mentally retarded and many also exhibit repetitious hand and body movements. Roughly one in 500 persons may be affected by autism or a related disorder.

The researchers tested blood samples collected from 57 people diagnosed with autism to determine if they possessed a variant form of the HOXA1 gene. Of these, 22 people - about 40 percent-had one copy of the variant gene. 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 and Dentistry. When hundreds of people without autism were tested, people with two copies were even less common. This suggests that most people who have two copies of the gene die early in life, perhaps before birth.

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 aberrant 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 role 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.

The origin of autism has been difficult to identify because there is no single cause. Several genes, as well as fetal exposure to toxic chemicals early in pregnancy, are thought to play a role. Identifying the HOXA1 gene as a culprit could be the first step toward developing strategies to treat and prevent the disorder.

The research team also included Jennifer Ingram, Ph.D., Christopher Stodgell, Ph.D., Susan Hyman, M.D., Denise Figlewicz, Ph.D., and Lowell Weitkamp, M.D., of the University of Rochester School of Medicine and Dentistry in Rochester, New York. The University of Rochester was designated by the National Institutes of Health as a Collaborative Center of Excellence in Autism, one of 10 such centers in the nation. The centers are part of a $42 million initiative aimed at unraveling the mysteries of autism.

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