Gene tests can provide health clues

NEW YORK — Last year, Katie Burns got a phone call that shows what can happen in medicine when information runs ahead of knowledge.

Burns learned that a genetic test of her fetus had turned up an abnormality. It appeared in a gene that, when it fails to work properly, causes heart defects, mental disability and other problems. But nobody knew whether the specific abnormality detected by the test would cause trouble.

“I was pretty distraught,” said Burns, a photographer in Charlotte, North Carolina. “I had a baby who was kicking. I could feel him moving inside of me. But at the same time I had this ache in my chest. What was his life going to be for him?”

It took two months to get more reliable information, and Burns said she wasn’t really

sure of the answer until after she gave birth in October to a healthy boy.

Her experience is a glimpse into a surprising paradox of modern-day genetics: Scientists have made huge leaps in rapidly decoding people’s DNA, but they sometimes don’t know what their findings mean. They can even get fooled.

That can come to a head when medical professionals have people tested for genetic variants that cause or promote a disease, usually because they show symptoms or an illness runs in their family. The testing often focuses on relatively rare disorders, caused by a single gene.

Medicine is getting into genetic testing in a big way. One recent estimate found nearly 75,000 health-related DNA tests being marketed by American labs to health care providers, mostly for single-gene disorders, with the total growing rapidly. And this year, the Pennsylvania-based Geisinger health system began offering free genetic testing to its patients as a standard part of its disease prevention efforts, along with things like mammograms and cholesterol checks.

Americans are interested in what their genes say about their health. Poll results found that 60 percent would want to know if they carried a variant associated with even an incurable disease.

But DNA test results can be puzzling. Katie Burns’ fetus had what experts call a “variant of uncertain significance,” or a VUS. Many are known: One standard database contains almost 193,000 variants categorized as a VUS, more than twice the number of listed variants known to cause disease.

Each variant may be seen in only one or a handful of patients. But as a group, many thousands of them are being reported to patients, said Heidi Rehm of Boston’s Massachusetts General Hospital.

The rates vary by disease. In seeking genes to explain a patient’s hearing loss, for example, around half of tests will find only a VUS, she said. A child with symptoms that suggest developmental delay or a related disorder might get a test that examines 200 genes, she said. With such a wide net cast, the chances of a VUS are nearly 100 percent, she said.

Scientists do have ways to determine if a variant is risky or not, but they often don’t have enough information to make the call. As scientists find more people with a VUS and carry out lab studies, they hope to distinguish the truly risky ones from those that are harmless. With large population databases that have recently become available, they can determine if a VUS is more common in the general population than the rare disease it might cause — a sign that it’s harmless.

Meanwhile, any worried parent who consults Clinvar about the genetic variant found in Katie Burns’ baby will find a bit of comfort.

In November, after hearing the good news from the Burns family, Rehm updated the database to note that her lab no longer considered it a VUS.

The new classification: “Likely benign.”