title: Primary congenital glaucoma and Rieger's anomaly: extended haplotypes reveal founder effects for eight distinct CYP1B1 mutations.
abstract: OBJECTIVE
  Mutations in the cytochrome P450 1B1 (CYP1B1) gene are a frequent cause of primary congenital glaucoma (PCG) in different ethnic groups. Cytochrome P450 proteins are monooxygenases, which catalyze many reactions involved in the metabolism of drugs as well as steroids and other lipids. The repeated occurence of several mutations in various ethnic groups raises the question if founder effects or mutation-prone sites in CYP1B1 are the cause for this observation.
  
  
  METHODS
  A total of 30 individuals (26 PCG patients, three Rieger's anomaly patients, and one variant carrier), presenting 17 variants in CYP1B1 (15 mutations and two variations) were included in our study. We sequenced the entire genomic region of CYP1B1 and analyzed microsatellites flanking the gene in all individuals and constructed haplotypes for all variations using a combination of single nucleotide polymorphisms and microsatellites.
  
  
  RESULTS
  For the CYP1B1 genomic region, we identified five extended haplotypes associated with 17 variations. These haplotypes were complemented with microsatellite information from the region surrounding this gene. A total of eight CYP1B1 mutations were found more than once, each of them presenting one identical haplotype in different individuals. Six mutations were represented in different ethnic groups.
  
  
  CONCLUSIONS
  Our results confirm founder effects for most of CYP1B1 mutations. Most of these mutations must have occurred as unique events in the past.
authors.affiliation: Institute of Human Genetics, Friedrich-Alexander-University, Erlangen, Germany.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Chavarria-Soley
authors.forename: Karin
authors.initials: K
authors.lastname: Michels-Rautenstrauss
authors.forename: Francesca
authors.initials: F
authors.lastname: Pasutto
authors.forename: David
authors.initials: D
authors.lastname: Flikier
authors.forename: Paul
authors.initials: P
authors.lastname: Flikier
authors.forename: Sebahattin
authors.initials: S
authors.lastname: Cirak
authors.forename: Bassem
authors.initials: B
authors.lastname: Bejjani
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Winters
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lewis
authors.forename: Christian
authors.initials: C
authors.lastname: Mardin
authors.forename: Andre
authors.initials: A
authors.lastname: Reis
authors.forename: Bernd
authors.initials: B
authors.lastname: Rautenstrauss
mesh_terms: D000869:Anterior Eye Segment / Q000002:abnormalities*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001483:Base Sequence; D065633:Cytochrome P-450 CYP1B1; D005124:Eye Abnormalities / Q000235:genetics*; D018703:Founder Effect; D005901:Glaucoma / Q000151:congenital* / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D018895:Microsatellite Repeats; D009154:Mutation
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1