Cause of Port-Wine-Stain Birthmarks Pinpointed
Single, random change to gene during fetal development causes birthmarks and the more serious Sturge-Weber syndrome
Ball met Pevsner at a conference sponsored by the U.S. National Institutes of Health in 1999. There, doctors said they would need tissue samples if they were to discover the roots of the condition.
Ball began to urge parents to contribute to a collection of samples.
"That was a hard sell for parents, because they didn't want to scar their baby on top of the birthmark, so you have to walk them through that psychological process [of donating tissue]," she said.
They didn't yet know what kinds of tests doctors might need to run, so some of the samples were preserved in paraffin wax while others were frozen or stored in saline.
"The donated samples were essential to the success of the research," Comi said.
For the study, researchers sequenced the entire genome -- 3 billion base pairs of DNA -- from samples of tissue taken from three different patients. Half of the samples were from affected areas of skin or brain tissue while the other half were from normal, healthy tissue from the same patients.
Out of 700 billion base pairs of DNA, there was only a single spot that was consistently changed between affected and unaffected samples.
"It's a needle in a million haystacks [to find that]," Pevsner said.
Once they found the change, they searched for it in 97 other samples of patients with Sturge-Weber syndrome or port-wine stains, and healthy patients who didn't have either.
Nearly all the patients with Sturge-Weber syndrome or port-wine stains had the mutation in affected areas of the skin or brain. Researchers almost never found the mutation on visibly normal skin or in people with neither the birthmark nor the syndrome.
The mutation is in the GNAQ gene, which makes a protein that is critical for cell signaling.
Researchers think that when the mutation happens very early in a baby's development, it may lead to the more severe Sturge-Weber syndrome. When it happens later, it causes port-wine stains, which can be disfiguring but usually don't lead to more extensive health issues.
Now that they have identified the mutation, doctors can start to look for drugs that will treat some of the problems it causes. Current treatments for Sturge-Weber aim to control symptoms, but don't always do the job.
"In half or more of the patients, their seizures are not fully or well-controlled," Comi said. "We have low-dose aspirin to try to prevent strokes. We're able to help the children, but we're certainly not able to prevent all the neurologic and ophthalmologic consequences of the condition."
Perhaps the most immediate consequence of the discovery may be that it lessens the guilt felt by many parents who believe they somehow caused their children's condition by passing it to them genetically.