Investigators from Johns Hopkins School of Medicine, the Hugo W Moser Research Institute at Kennedy Krieger, Baltimore; Duke University; and Medical College of Wisconsin, Milwaukee, performed whole-genome sequencing of DNA from paired samples of tissue from 3 persons with the Sturge-Weber syndrome (SWS). GNAQ somatic mosaic mutations were identified in 88% of participants (23 of 26) with the SWS and from 92% of participants (12 of 13) with nonsyndromic port-wine stains, but not in any of samples from 4 participants with an unrelated cerebrovascular malformation or in any of the samples from 6 controls. The prevalence of the mutant allele in affected tissues ranged from 1.0 to 18.1%. SWS and port-wine stains are caused by a somatic activating mutation in GNAQ. [1]

COMMENT. These findings identify a single mechanism for the SWS and nonsyndromic port-wine stains and they document a molecular basis for these malformations, causally related to a mutation in a specific gene, GNAQ. The authors hypothesize that the port-wine stains may represent a late origin of the somatic GNAQ mutation in vascular endothelial cells, whereas the SWS mutation may occur earlier in embryotic development. A child born with a port-wine stain in the distribution of the ophthalmic branch of the trigeminal nerve has a 26% chance of having SWS. [2]