title: Novel genetic mutations in a sporadic port-wine stain.
abstract: IMPORTANCE Port-wine stains (PWSs) are common congenital cutaneous capillary malformations. A somatic GNAQ mutation was recently identified in patients with sporadic PWSs and Sturge-Weber syndrome. However, subsequent studies to confirm or extend this observation are lacking.OBSERVATIONS We report a long-standing, unilateral facial PWS of a man in his early 70s confirmed by histopathological analysis. Staged surgical excision of the vascular malformation was performed, and genomic DNA was extracted from the vascular malformation specimen and normal skin. Targeted next-generation sequencing of the coding sequence of 275 known cancer genes including GNAQ was performed in both specimens. A single-nucleotide variant(c.548G>A, p.Arg183Gln) in GNAQ was identified in the PWS-affected tissue but not in the normal skin sample. In addition, this sequencing approach uncovered several additional novel somatic mutations in the genes SMARCA4, EPHA3, MYB, PDGFR-β, and PIK3CA.CONCLUSIONS AND RELEVANCE Our findings confirm the presence of somatic mutations inGNAQ in the affected skin of a patient with congenital PWS, as well as alterations in several other novel genes of possible importance in the pathogenesis of PWS that may also offer substantial therapeutic targets.
authors.forename: Christine Guo
authors.initials: CG
authors.lastname: Lian
authors.forename: Lynette M
authors.initials: LM
authors.lastname: Sholl
authors.forename: Labib R
authors.initials: LR
authors.lastname: Zakka
authors.forename: Teresa M
authors.initials: TM
authors.lastname: O
authors.forename: Cynthia
authors.initials: C
authors.lastname: Liu
authors.forename: Shuyun
authors.initials: S
authors.lastname: Xu
authors.forename: Ewelina
authors.initials: E
authors.lastname: Stanek
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Garcia
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Jia
authors.forename: Laura E
authors.initials: LE
authors.lastname: MacConaill
authors.forename: George F
authors.initials: GF
authors.lastname: Murphy
authors.forename: Milton
authors.initials: M
authors.lastname: Waner
authors.forename: Martin C
authors.initials: MC
authors.lastname: Mihm
mesh_terms: D000368:Aged; D058534:Class I Phosphatidylinositol 3-Kinases; D004265:DNA Helicases / Q000235:genetics; D005148:Facial Dermatoses / Q000235:genetics*; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020570:Genes, myb / Q000235:genetics; D006801:Humans; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D019339:Port-Wine Stain / Q000235:genetics* / Q000601:surgery; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D036121:Receptor, EphA3; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; D004265:DNA Helicases; D044385:GTP-Binding Protein alpha Subunits; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D009687:Nuclear Proteins; D019869:Phosphatidylinositol 3-Kinases; D020794:Receptor Protein-Tyrosine Kinases; D036121:Receptor, EphA3; D020797:Receptor, Platelet-Derived Growth Factor beta; D014157:Transcription Factors; C554061:GNAQ protein, human; C484760:PIK3CA protein, human; C491718:EPHA3 protein, human; C084108:SMARCA4 protein, human