Homing In On a Gene for Down Syndrome

San Francisco--Scientists have discovered a gene that may cause two key symptoms--mental retardation and nearsightedness--of Down syndrome. The findings were reported here today at the American Society for Cell Biology's annual meeting.

About one in 800 U.S. newborns develops Down syndrome, a condition without a cure whose most disabling symptom is often profound mental retardation. People with Down syndrome have an extra copy or extra piece of chromosome 21, including a gene called DYRK whose protein appears to be critical to the growth of nerve cells in the brain.

Molecular biologist Woo-Joo Song of the University of Michigan Medical Center in Ann Arbor knew that fruit flies lacking a copy of a similar gene develop abnormal brains and learning problems. He and groups elsewhere in the United States, Spain, and Japan have independently used the DNA sequence of the fruit fly version of DYRK, called minibrain, as a probe to find similar sequences in mouse and human cells. During development, the mouse version is most active in gray matter, the spinal cord, and the retina--regions that are defective in people with Down syndrome, Song reported in San Francisco. "The patterns [of gene activity] may partially explain some of the [symptoms] of Down syndrome," he says.

One of the other teams hot on DYRK's trail is a duo from the Lawrence Berkeley National Laboratory, molecular biologists Edward Rubin and Desmond Smith. They have spliced a section of human chromosome 21 containing DYRK into developing mice and found that it caused learning deficits. "We're still short of a final proof," says Smith, "but there are enough intriguing parallels that suggest this [gene] may be involved in the learning deficits in Down syndrome." It turns out that the amount of the gene's protein present in cells is critical: Too little results in learning disabilities in the fruit fly, while it appears that too much results in similar symptoms in mice and people.

Other genes, Smith says, are likely responsible for abnormalities in the skeletons, digestive systems, and hearts of people with Down syndrome. Both teams say their results are too preliminary to suggest any obvious therapies.