title: Novel CYP1B1 mutations in consanguineous Pakistani families with primary congenital glaucoma.
abstract: OBJECTIVE
  To identify the disease-causing mutations in three consanguineous Pakistani families with multiple members affected by primary congenital glaucoma.
  
  
  METHODS
  Blood samples were collected, and DNA was extracted. Linkage analysis for reported primary congenital glaucoma loci was performed using closely spaced polymorphic microsatellite markers on genomic DNA from affected and unaffected family members. All coding exons, the exon-intron boundaries, and the 5' untranslated region of CYP1B1 were sequenced.
  
  
  RESULTS
  The alleles of chromosome 2p markers segregate with the disease phenotype in all three families with positive LOD scores. The sequencing results identified three novel mutations (L177R, L487P, and D374E) and one previously reported mutation (E229K) in CYP1B1 that segregate with the disease phenotype in their respective families. None of these sequence variations were present in 96 ethnically matched control samples.
  
  
  CONCLUSIONS
  These results strongly suggest that missense mutations in CYP1B1 are most likely to be responsible for primary congenital glaucoma in these families.
authors.affiliation: National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
authors.forename: Sabika
authors.initials: S
authors.lastname: Firasat
authors.forename: S Amer
authors.initials: SA
authors.lastname: Riazuddin
authors.forename: Shaheen N
authors.initials: SN
authors.lastname: Khan
authors.forename: Sheikh
authors.initials: S
authors.lastname: Riazuddin
mesh_terms: D000595:Amino Acid Sequence; D001189:Aryl Hydrocarbon Hydroxylases; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D003241:Consanguinity; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000235:genetics*; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D005901:Glaucoma / Q000151:congenital* / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D008126:Lod Score; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010154:Pakistan; D010375:Pedigree; D016415:Sequence Alignment
chemical_list: D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1