Frigerio, AliceWright, KarolWooderchak-Donahue, WhitneyTan, OonMargraf, RebeccaStevenson, David A.Grimmer, J. FredrikBayrak-Toydemir, Pinar2015-08-032015Frigerio, Alice, Karol Wright, Whitney Wooderchak-Donahue, Oon T. Tan, Rebecca Margraf, David A. Stevenson, J. Fredrik Grimmer, and Pinar Bayrak-Toydemir. 2015. “Genetic Variants Associated with Port-Wine Stains.” PLoS ONE 10 (7): e0133158. doi:10.1371/journal.pone.0133158. http://dx.doi.org/10.1371/journal.pone.0133158.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:17820939Background: Port-wine stains (PWS) are capillary malformations, typically located in the dermis of the head and neck, affecting 0.3% of the population. Current theories suggest that port-wine stains are caused by somatic mutations that disrupt vascular development. Objectives: Understanding PWS genetic determinants could provide insight into new treatments. Methods: Our study used a custom next generation sequencing (NGS) panel and digital polymerase chain reaction to investigate genetic variants in 12 individuals with isolated port-wine stains. Importantly, affected and healthy skin tissue from the same individual were compared. A subtractive correction method was developed to eliminate background noise from NGS data. This allowed the detection of a very low level of mosaicism. Results: A novel somatic variant GNAQ, c.547C>G, p.Arg183Gly was found in one case with 4% allele frequency. The previously reported GNAQ c.548G>A, p.Arg183Gln was confirmed in 9 of 12 cases with an allele frequency ranging from 1.73 to 7.42%. Digital polymerase chain reaction confirmed novel variants detected by next generation sequencing. Two novel somatic variants were also found in RASA1, although neither was predicted to be deleterious. Conclusions: This is the second largest study on isolated, non-syndromic PWS. Our data suggest that GNAQ is the main genetic determinant in this condition. Moreover, isolated port-wine stains are distinct from capillary malformations seen in RASA1 disorders, which will be helpful in clinical evaluation.en-USJournal Article2015-08-0310.1371/journal.pone.0133158