Ataxia telangiectasia

Some toddlers toddle a lot not because of their youth, but because they have inherited a fatal neurological disorder, ataxia-telangiectasia (A-T). These children also suffer from involuntary movements and slurred speech. Moreover, they and perhaps their parents, who are carriers of A-T, face a higher than normal risk of cancer.

Now, researchers announce that mutations in a key segment of a single gene cause the disease. Earlier studies had suggested that A-T results from mutations of several genes.

"The identification of a single gene responsible for A-T should enable clinical geneticists to offer reliable diagnostic tests, including prenatal diagnosis and carrier detection to all A-T families," report Yosef Shiloh of the Sackler School of Medicine at Tel Aviv University and his colleagues in the June 23 Science. In the past year, he and his colleagues have tested a prenatal screen that he expects will now find broad use.

When both members of a couple carry the A-T mutated (ATM) gene, their children have a one in four chance of having the disease. Between 1 in 40,000 and 1 in 100,000 people develop the disorder. Certain groups, including Italians and Turks, have the higher incidence. A-T carriers, who inherit the defective gene from only one parent and don't develop the disease, form about 1 percent of the U.S. population.

A-T patients suffer from weak immune systems and premature aging, among other ills, and usually die in their teens or early twenties. Patients, and to a lesser degree carriers, are sensitive to ionizing radiation. Other studies have suggested that carriers face roughly four times the general population's risk of getting cancer. In addition, women may have six times the normal risk of breast cancer (SN: 1/4/92, p.4).

Discovery of the ATM gene segment will enable scientists to test "whether or not female or male carriers of this disease are at an increased risk of developing cancer," says David L. Nelson of the National Cancer Institute in Bethesda, Md. Studies have yet to prove that carriers have a heightened chance of getting cancer, he argues.

Efforts to develop a treatment for A-T and to learn more about how cancer develops will also benefit from the gene discovery, scientists say.

The gene's protein resembles phosphatidylinositol-3 kinase (PI-3 kinase) and other well-known enzymes involved in immune function, cell death, and cell division, says Shiloh. Information about those enzymes should help researchers in their pursuit of a treatment for A-T, says Nathaniel Heintz, a Howard Hughes Medical Institute investigator at Rockefeller University in New York City.

Studying ATM will also shed light on the possible link--which researchers are just now making--between the body's control of both cell division and cell death, says Heintz. A-T patients suffer from rapid loss of brain cells as well as from tumors.

COPYRIGHT 1995 Science Service, Inc.
COPYRIGHT 2004 Gale Group