title: Endothelial Cells from Capillary Malformations Are Enriched for Somatic GNAQ Mutations.
abstract: BACKGROUND
  A somatic mutation in GNAQ (c.548G>A; p.R183Q), encoding Gαq, has been found in syndromic and sporadic capillary malformation tissue. However, the specific cell type containing the mutation is unknown. The purpose of this study was to determine which cells in capillary malformations have the GNAQ mutation.
  
  
  METHODS
  Human capillary malformation tissue was obtained from 13 patients during a clinically indicated procedure. Droplet digital polymerase chain reaction, capable of detecting mutant allelic frequencies as low as 0.1 percent, was used to quantify the abundance of GNAQ mutant cells in capillary malformation tissue. Six specimens were fractionated by fluorescence-activated cell sorting into hematopoietic, endothelial, perivascular, and stromal cells. The frequency of GNAQ mutant cells in these populations was quantified by droplet digital polymerase chain reaction.
  
  
  RESULTS
  Eight capillary malformations contained GNAQ p.R183Q mutant cells, two lesions had novel GNAQ mutations (p.R183L and p.R183G), and three capillary malformations did not have a detectable GNAQ p.R183 mutation. Mutant allelic frequencies ranged from 2 to 11 percent. Following fluorescence-activated cell sorting, the GNAQ mutation was found in the endothelial but not the platelet-derived growth factor receptor-β-positive cell population; mutant allelic frequencies were 3 to 43 percent.
  
  
  CONCLUSIONS
  Endothelial cells in capillary malformations are enriched for GNAQ mutations and are likely responsible for the pathophysiology underlying capillary malformation.
authors.affiliation: Boston, Mass. From the Departments of Plastic and Oral Surgery, Surgery, and Orthopedic Surgery, Vascular Anomalies Center, Vascular Biology Program, and the Howard Hughes Medical Institute, Boston Children's Hospital; and the Department of Genetics, Harvard Medical School.
authors.forename: Javier A
authors.initials: JA
authors.lastname: Couto
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Vivero
authors.forename: Nolan
authors.initials: N
authors.lastname: Kamitaki
authors.forename: Reid A
authors.initials: RA
authors.lastname: Maclellan
authors.forename: John B
authors.initials: JB
authors.lastname: Mulliken
authors.forename: Joyce
authors.initials: J
authors.lastname: Bischoff
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Warman
authors.forename: Arin K
authors.initials: AK
authors.lastname: Greene
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D002196:Capillaries / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology; D002648:Child; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D054079:Vascular Malformations / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: C584143:GNAO1 protein, human; D004247:DNA; D019206:GTP-Binding Protein alpha Subunits, Gi-Go