This article is more than 5 years old. Information may no longer be current.

Port-wine stains, Sturge-Weber syndrome caused by GNAQ mutation

A somatic activating mutation in GNAQ causes Sturge-Weber syndrome and port-wine stains, according to recent study results.

Researchers used paired samples of visibly affected and normal tissue from three patients with Sturge-Weber syndrome, a sporadic congenital neurocutaneous disorder consisting of a port-wine stain distributed over the trigeminal nerve, to perform whole-genome sequencing of DNA. Amplicon sequencing and SNaPshot assays were used to test 97 samples from 50 patients with Sturge-Weber syndrome, a port-wine stain or neither (controls) for somatic mosaic mutation. Phosphorylation antibodies for relevant effectors and luciferase reporter assay were used to investigate effects of the mutation on downstream signaling.

Samples of affected tissue in 88% of patients with Sturge-Weber syndrome and 92% of patients with nonsyndromic port-wine stains contained nonsynonymous single-nucleotide variant (c.548G[A], p.Arg183Gln) in GNAQ. Samples from four patients with unrelated cerebrovascular malformation and from the six control patients excluded the variant.

“The prevalence of the mutant allele in affected tissues ranged from 1% to 18.1%,” the researchers reported.

Transgenic expression of mutant Ga_q caused a modest increase in extracellular signal-related kinase activity.

“Our data indicate that there is a single underlying mechanism for the Sturge-Weber syndrome and nonsyndromic port-wine stains and add a molecular basis for a decades-old hypothesis regarding the cause of these malformations,” the researchers concluded. “The scientific and translational novelty of this discovery lies in the association of both apparently nonsyndromic port-wine stains and the Sturge-Weber syndrome with a mutation in a specific gene, a specific genetic mechanism, and a set of potential pathways, which provides a foundation for further scientific and clinical research.”