title: Novel CYP1B1 and known PAX6 mutations in anterior segment dysgenesis (ASD).
abstract: OBJECTIVE
  The study intended to define the underlying genetic defects for 21 index patients affected with different forms of anterior segment dysgenesis. Sequence analysis for the PAX6, PITX2, FOXC1, and CYP1B1 genes has been implemented for this purpose.
  
  
  METHODS
  Ten patients affected with Peters anomaly, 8 with Rieger anomaly, and 3 with aniridia were included in this study. All patients underwent a complete eye examination, including anterior segment evaluation, with slit-lamp microsocopy, fundoscopy, tonography, and gonioscopy. Twenty-one intronic primer pairs were used to amplify the coding exons of the FOXC1, CYP1B1, PITX2, and PAX6 genes for sequence analysis on an automated sequencer (ABI 3730).
  
  
  RESULTS
  We were able to detect mutations in 5 of 21 patients with anterior segment malformations. We found mutations in individuals suffering from Rieger anomaly and aniridia, in CYP1B1 and PAX6, respectively. None of the 10 Peters anomaly patients had causative mutations in any of the 4 genes we screened.
  
  
  CONCLUSIONS
  Our results suggest primary congenital glaucoma and the anterior segment dysgenesis disorders may share a common molecular pathophysiology in the CYP1B1 pathway.
authors.affiliation: Institute of Human Genetics, Schwabachanlage 10, 91054 Erlangen, Germany.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Chavarria-Soley
authors.forename: Karin
authors.initials: K
authors.lastname: Michels-Rautenstrauss
authors.forename: Almuth
authors.initials: A
authors.lastname: Caliebe
authors.forename: Monika
authors.initials: M
authors.lastname: Kautza
authors.forename: Christian
authors.initials: C
authors.lastname: Mardin
authors.forename: Bernd
authors.initials: B
authors.lastname: Rautenstrauss
mesh_terms: D000595:Amino Acid Sequence; D000869:Anterior Eye Segment / Q000002:abnormalities*; D001189:Aryl Hydrocarbon Hydroxylases; D001483:Base Sequence; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004252:DNA Mutational Analysis; D005124:Eye Abnormalities / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D051858:Forkhead Transcription Factors / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics*; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics; D000097577:Homeobox Protein PITX2
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System; D005136:Eye Proteins; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2; C112743:FOXC1 protein, human; C000605730:PAX6 protein, human; C585496:CYP1B1 protein, human