Genetic mutations cause port wine stains

Researchers have identified the underlying genetic mutation responsible for port wine stains and Sturge-Weber syndrome, which may allow for the development of more targeted therapies.

Investigators with Kennedy Krieger Institute, Baltimore, identified the somatic mutation responsible for Sturge-Weber syndrome (SWS) and port wine stains after performing whole genome sequencing on affected and unaffected tissue and blood samples from three patients with SWS. A nucleotide transition in gene GNAQ on chromosome 9q21 was shared by all three affected samples. The researchers confirmed their finding by detecting this mutation in 23 of 26 tissues samples from patients with SWS and in 12 of 13 samples from patients with port wine stains.

“The control samples, and most of the unaffected samples, did not possess the mutation,” according to a news release. “These analyses also revealed the surprising outcome that the gene involved in SWS is the same gene implicated in uveal melanoma.”

Scientists from Duke University Medical Center, Durham, N.C., collaborated in the study and found that GNAQ encodes a set of membrane proteins that ensure signaling pathways within the cell work properly, according to the news release.

The revelation that SWS is caused by a somatic mutation enabled investigators to confirm that the syndrome is not inherited. The study findings should also allow researchers to begin looking into drugs that selectively inhibit implicated pathways.

“This study presents a turning point for research on Sturge-Weber syndrome and port wine birthmarks. While we suspected that a somatic mutation was the cause for decades now, the technology to test the theory didn’t exist,” Jonathan Pevsner, Ph.D., co-senior author of the study and director of bioinformatics at Kennedy Krieger Institute, stated in the news release. “The advancements in whole genome sequencing and the development of next-generation sequencing tools finally allowed my lab to test and prove the hypothesis.”

The study was published online May 8 in the New England Journal of Medicine.