title: Genotype and phenotype correlations in congenital glaucoma: CYP1B1 mutations, goniodysgenesis, and clinical characteristics.
abstract: OBJECTIVE
  To determine whether there is a correlation among mutations in the cytochrome P4501B1 gene (CYP1B1), the degree of angle dysgenesis observed histologically, and disease severity in congenital glaucoma.
  
  
  METHODS
  Interventional case series.
  
  
  METHODS
  Direct DNA sequencing was used to screen six unrelated children with congenital glaucoma, each set of parents, and all siblings for CYP1B1 mutations. Specimens of the anterior chamber angle obtained at trabeculectomy were examined histologically to identify abnormalities of the aqueous outflow pathway. CYP1B1 mutations were correlated with both the degree of angle dysgenesis and the patients' disease severity (age at diagnosis, difficulty in achieving intraocular pressure [IOP]) control.
  
  
  RESULTS
  Four (66.7%) of the six patients were compound heterozygotes for mutations in the CYP1B1 gene. Seven of the eight CYP1B1 mutations were identified, including two novel mutations (R117P, C209R) and five others previously described (G61E, R368H, R390H, E229K, 4340delG). The cases were divided on the basis of histological phenotype into categories of (1) severe goniodysgenesis highlighted by the agenesis of the canal of Schlemm (two patients), (2) moderate goniodysgenesis characterized by the presence of a band of collagenous tissue (CT) in the trabecular meshwork (TM) and/or the juxtacanalicular tissues (JXT) (three patients), and (3) mild goniodysgenesis with deposition of a mucopolysaccharide material in the JXT (one patient). CYP1B1 mutations were identified in both cases of severe angle dysgenesis and two of three cases of moderate dysgenesis. Disease severity closely correlated with the degree of angle dysgenesis.
  
  
  CONCLUSIONS
  Most patients in our cohort had compound heterozygous CYP1B1 mutations. Specific CYP1B1 mutations may be associated with severe or moderate angle abnormalities.
authors.affiliation: Glaucoma Research Laboratory, Department of Ophthalmology, University of California, San Francisco, California 94143-073, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Hollander
authors.forename: Mansoor
authors.initials: M
authors.lastname: Sarfarazi
authors.forename: Ivaylo
authors.initials: I
authors.lastname: Stoilov
authors.forename: Irmgard S
authors.initials: IS
authors.lastname: Wood
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Fredrick
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Alvarado
mesh_terms: D000867:Anterior Chamber / Q000002:abnormalities / Q000473:pathology; D001189:Aryl Hydrocarbon Hydroxylases; D002924:Ciliary Body / Q000002:abnormalities / Q000473:pathology; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004252:DNA Mutational Analysis; D005124:Eye Abnormalities / Q000235:genetics* / Q000473:pathology; D005260:Female; D005838:Genotype; D005901:Glaucoma / Q000151:congenital* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007429:Intraocular Pressure; D007498:Iris / Q000002:abnormalities / Q000473:pathology; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D014129:Trabecular Meshwork / Q000002:abnormalities / Q000473:pathology / Q000601:surgery; D014130:Trabeculectomy
chemical_list: D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1