title: Sturge-Weber syndrome with congenital glaucoma and cytochrome P450 (CYP1B1) gene mutations.
abstract: Sturge-Weber syndrome (SWS) is a progressive condition of mesodermal phakomatosis. This preliminary study is the first report of CYP1B1 mutation analysis in SWS with congenital glaucoma.
  
  
  OBJECTIVE
  Mutations in CYP1B1 gene are the major cause of congenital glaucoma. CYP1B1 is involved in metabolism of melatonin, retinol, and other endogenous/exogenous substrates. Mutations in CYP1B1 adversely affect signal transduction pathways and thus impair development/differentiation of anterior segment structures. This results in impaired aqueous outflow. CYP1B1 has higher expression in fetal eyes and plays major role in morphogenesis of iris, ciliary body, and anterior chamber angle. Hence, we decided to evaluate SWS cases with buphthalmos for 6 most prevalent CYP1B1 mutations by polymerase chain reaction-restriction-fragment length polymorphism followed by sequencing. Trabecular meshwork was studied for morphological alterations by scanning electron microscopy.
  
  
  RESULTS
  All patients had normal 46, XY karyotype. Polymerase chain reaction-restriction-fragment length polymorphism showed CYP1B1 mutations in 2 of 5 SWS cases. Scanning electron microscopy findings were suggestive of trabecular dysgenesis.
  
  
  CONCLUSIONS
  No CYP1B1 mutation has been reported in any SWS case till date because syndromic cases were not analyzed for mutations in earlier studies. Earlier studies have reported that onset of glaucoma in SWS shows a bimodal pattern. The results from this pilot study show that SWS cases with gyral calcification, buphthalmos, and early onset glaucoma should be analyzed for CYP1B1 mutations. The effect of vascular malformation-induced venous engorgement and raised intraocular pressure may only be additive and may result in a much more severe phenotype.
  
  
  CONCLUSIONS
  SWS with buphthalmos and gyral calcification should undergo CYP1B1 mutation analysis to identify an underlying genetic pathology for glaucoma. This will aid in determining the prognosis and management and will also help to provide comprehensive counseling in such cases.
authors.affiliation: Department Of Anatomy, Laboratory for Molecular Reproduction and Genetics, AIIMS, Ansari Nagar, New Delhi 110029, India.
authors.forename: Mukesh
authors.initials: M
authors.lastname: Tanwar
authors.forename: Ramanjit
authors.initials: R
authors.lastname: Sihota
authors.forename: Tanuj
authors.initials: T
authors.lastname: Dada
authors.forename: Vinay
authors.initials: V
authors.lastname: Gupta
authors.forename: Taposh K
authors.initials: TK
authors.lastname: Das
authors.forename: Usha
authors.initials: U
authors.lastname: Yadav
authors.forename: Rima
authors.initials: R
authors.lastname: Dada
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases; D002114:Calcinosis / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004252:DNA Mutational Analysis; D006068:Gonioscopy; D006801:Humans; D006871:Hydrophthalmos / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D007223:Infant; D007429:Intraocular Pressure; D008279:Magnetic Resonance Imaging; D008297:Male; D008855:Microscopy, Electron, Scanning; D009154:Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D013341:Sturge-Weber Syndrome / Q000175:diagnosis / Q000235:genetics*; D014065:Tonometry, Ocular; D014129:Trabecular Meshwork / Q000648:ultrastructure; D014130:Trabeculectomy
chemical_list: D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1