Gene implicated in development of autism

A new lead has emerged in the search for genetic influences on autism. A variant of a gene known as HOXA1, which supervises fetal-brain development, may predispose people to develop autism or several related disorders, according to a report in the December Teratology.

“I suspect that there are quite a few gene variants that confer a susceptibility to autism,” says embryologist Patricia M. Rodier of the University of Rochester (N.Y.) School of Medicine and Dentistry, who directed the investigation. Even when such variants are present, however, protective genes or environmental factors probably often prevent the emergence of autism, Rodier adds.

Rodier’s group studied 40 people with autism and 17 people with any of three other autismlike disorders. Problems in communication and social interaction characterize all these conditions. Autism also frequently includes mental retardation and repetitious body movements.

In a DNA analysis, 22 of the 57 participants—about 40 percent—exhibited the HOXA1 variant. HOXA1 helps regulate other genes that direct the formation of the brain stem, a structure that has attracted little attention from autism researchers. In 21 of those 22 cases, individuals carried one copy of the variant and one copy of a more common version. Only one person displayed two copies of the variant.

About 20 percent of more than 200 people in a group with no neurological or psychiatric diagnoses have a copy of the HOXA1 variant, Rodier’s team found.

The team also examined 166 of the 57 participants’ relatives, including many parents and siblings. Of the relatives, 32 people met the researchers’ criteria for having autism, related disorders, or a severe language delay. The HOXA1 variant again appeared in about 40 percent of these people and less frequently in the other relatives.

In 68 cases, genetic data were available for both parents of a participant or a relative. Autism symptoms appeared far more often in those who inherited the aberrant gene from their mother than from their father, the researchers found.

Rodier and her coworkers conducted their research as part of an international network of 10 teams exploring autism’s roots with funding by the National Institutes of Health in Bethesda, Md. The Rochester group focused on the HOXA1 gene after noting that mice whose HOXA1 gene had been experimentally knocked out of commission suffer physical defects similar to those in children exposed to thalidomide early in fetal life. In the view of Rodier’s group and some other researchers, those children sometimes develop autism along with ear and limb defects.

“Rodier’s finding is very interesting and clearly needs to be replicated,” comments psychiatrist Fred R. Volkmar of Yale University School of Medicine. Volkmar, a member of the NIH network, is participating in an effort to look for the HOXA1 variant in a larger sample of people with autism and related disorders.