Cause of Port-Wine-Stain Birthmarks Pinpointed
Single, random change to gene during fetal development causes birthmarks and the more serious Sturge-Weber syndrome
"When they gave me Kaelin, when she was a baby, she had a birthmark on her whole face," Ball said. "You feel all kinds of emotions at that moment too."
Beyond the birthmark, half of Kaelin's brain had hardened before birth and didn't work. Pressure was building up in her eyes, threatening her optic nerve. Doctors told the Balls that their daughter would likely have seizures and could lose her vision over time.
"Once I got over the pity party that I had -- 'Oh, she's never going to do this and she's never going to do that' -- then we geared up and said, 'All right, we're going to find out why this happened and make it better.'"
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.