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,” says 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 says 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.
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 and the Broad Institute in Cambridge.
Some variants lead to disease. But each of us carries many variants, and most are harmless. You can’t tell their effect just by looking at them. And just because a variant is rare, that doesn’t mean it’s harmful.
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. That’s what happened to Katie Burns.
She had the genetic test done because of an unusual finding on a fetal ultrasound scan. The VUS prompted her genetic counselor to suggest testing both her and her husband to see if they had the variant. The counselor also brought up the possibility of an abortion.
“Termination was off the table,” Burns said.
Instead, Burns scoured the internet. In a searchable database of genetic variants called Clinvar, she saw that Rehm’s laboratory had encountered the variant found in her fetus, and classified it as a VUS.
When Burns later learned that the variant appeared in her healthy husband, “a lot of stress kind of eased off.”
And in October, her son was born without any trace of the disease.
So how should a person react to a VUS? Genetic counselors say it should be considered along with the person’s other medical information, but not used as the sole reason for a major decision like breast removal.