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Lost in translation

Gene testing is proving to be a challenge: In one broad screening, results have been difficult to interpret, creating unintended risks.

May 12, 2003|Aaron Zitner | Times Staff Writer

Washington — Washington

Scientists have long promised that the gene revolution would bring new tests to tell whether a person is particularly vulnerable to cancer, heart disease, Alzheimer's disease and other ailments. By glimpsing the weaknesses coded in their genes, the reasoning has gone, people would be better equipped to alter their diet and behavior to avoid disease.

But the first major step toward these tests has gone awry in some cases, prompting questions about whether more federal regulation is needed and whether mass screening is even feasible for genetic predisposition to disease.

The problems have arisen in a test that tells people whether they carry DNA mutations for cystic fibrosis. In 2001, the American College of Obstetricians and Gynecologists recommended that doctors make the test available to every couple seeking care for a pregnancy or contemplating pregnancy so that they could determine the risk of producing a child with cystic fibrosis.

Because of the recommendation, cystic fibrosis screening has grown tenfold, to an estimated 200,000 to 400,000 tests annually. It is the first genetic test to be offered on a broad scale.

Now there is evidence that the test has sometimes done the opposite of what was intended, causing some people to add new risks to their pregnancies instead of helping them produce a healthy child.

In these cases, researchers say, confusion over how to interpret test results caused some people to believe mistakenly that their children were at risk for cystic fibrosis. As a result, some of them ordered amniocentesis or other fetal screening -- procedures that, while common, nonetheless present a small risk to the fetus.

In addition, the American College of Medical Genetics says it has received unconfirmed reports that some women aborted their pregnancies out of an erroneous belief that their children might have cystic fibrosis. Michael Watson, the group's executive director, said these reports were "anecdotal." Nonetheless, the group posted a "practice alert" at a March meeting saying that abortions in fact had occurred.

"This is heartbreaking. I'm deeply saddened," said Kathy Hudson, director of the Genetics and Public Policy Center at Johns Hopkins University in Baltimore. "This is not what was intended when we started this screening. You should get accurate information from the test, not information that is worrisome and anxiety-producing but doesn't have a whole lot to do with cystic fibrosis."

The test looks for mutations in a gene related to cystic fibrosis, the most common fatal genetic disease in the United States, affecting about 30,000 Americans. If both parents carry a mutation, each child has one chance in four of having cystic fibrosis.

In those cases, the prospective parents can opt to test their fetus for the disease. The information can help parents prepare to care for a sick child or, in some cases, lead them to end the pregnancy.

However, the genetics of cystic fibrosis are complex. The test looks for the 25 mutations of the cystic fibrosis gene. But other elements in the DNA can amplify the effects of some mutations, boosting the severity of the disease.

The mutation R117H, for example, can cause a mild form of cystic fibrosis, but only when it appears in tandem with one of these other DNA elements, known as 5T.

For laboratories, the easiest course would be to test for 5T at the same time they test for R117H and the other cystic fibrosis mutations. But the American College of Medical Genetics recommends against this. It says laboratories should first determine whether a patient has the R117H mutation, and then test for 5T in a second and separate test.

The reason is that 5T is very common -- appearing in 5% or more of the population -- and by itself causes no problems. Testing for it on a large scale would turn up thousands of people who had 5T but no cystic fibrosis mutation, "and you'd have them all worried about something that does not cause cystic fibrosis," said Dr. Wayne Grody, a UCLA genetics professor. By screening for R117H carriers first, laboratories would look for 5T only among patients who have a reason to worry about it.

However, one large laboratory, New Jersey-based Quest Diagnostics Inc., has been offering a test that includes 5T alongside the cystic fibrosis mutations.

This has led to some Quest clients being told that they had the 5T variation alone, with no R117H mutation -- information that the American College of Medical Genetics wanted to shield from patients.

Quest determined that at least 40 of these patients went on to request an amniocentesis or another test, even though they ran almost no risk of passing cystic fibrosis mutations to their children. The company said some of those patients would have ordered an amniocentesis anyway because of the age of the mother, but that 12 had no reason other than the 5T result for ordering the fetal test.

Quest publicized its study, alerting doctors to the problem.

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