title: Molecular analysis of the CYP1B1 gene: identification of novel truncating mutations in patients with primary congenital glaucoma.
abstract: BACKGROUND
  Mutations and polymorphisms have been identified in the CYP1B1 gene; while mutations that affect the conserved core structures of cytochrome P4501B1 result in primary congenital glaucoma (PCG), mutations in other regions hold the potential to define differences in estrogen metabolism. In the present study, we analyzed the CYP1B1 gene in Mexican patients with PCG and described four novel mutations.
  
  
  METHODS
  The sample included 12 nonrelated cases with PCG. Analysis of coding regions of the CYP1B1 gene was performed through PCR and DNA sequencing analysis from genomic DNA.
  
  
  CONCLUSIONS
  Molecular analysis of the CYP1B1 gene showed the following molecular defects: (1) a novel single-base pair deletion within codon 370 (1454delC) that produces a substitution of leucine instead of proline and a premature stop codon 57 amino acids after the last original amino acid; this family also harbored a novel polymorphic variant of the cytochrome P4501B1 with six single-nucleotide polymorphisms (142C-->G; 355G-->T; 729G-->C; 4326C-->G; 4360C-->G and 4379C-->T); (2) a novel single-base pair deletion within codon 277 (1176delT) that results in a premature stop codon; (3) a novel single-base pair deletion within codon 179 (880delG) that produces a substitution of arginine instead of alanine and a premature stop codon 17 amino acids downstream from the last original amino acid, and (4) a duplication (or insertion) of ten base pairs within codon 404 (1556dupATGCCACCAC) that results in a premature stop codon 26 amino acids after the last original amino acid. We also observed in 2 nonrelated patients a deletion of 13 bp (1410_1422delGAGTGCAGGCAGA) previously reported for other populations.
  
  
  CONCLUSIONS
  We reported four novel mutations and a novel polymorphic variant in the CYP1B1 gene in PCG in the Mexican population; it has important implications in diagnosis and genetic counseling.
authors.affiliation: Servicio de Oftalmología, Hospital General de México, Facultad de Medicina, UNAM, México, D.F., México.
authors.forename: O M
authors.initials: OM
authors.lastname: Messina-Baas
authors.forename: L M
authors.initials: LM
authors.lastname: González-Huerta
authors.forename: C
authors.initials: C
authors.lastname: Chima-Galán
authors.forename: S H
authors.initials: SH
authors.lastname: Kofman-Alfaro
authors.forename: M R
authors.initials: MR
authors.lastname: Rivera-Vega
authors.forename: I
authors.initials: I
authors.lastname: Babayán-Mena
authors.forename: S A
authors.initials: SA
authors.lastname: Cuevas-Covarrubias
mesh_terms: D000293:Adolescent; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004247:DNA / Q000032:analysis; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005901:Glaucoma / Q000151:congenital / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D011110:Polymorphism, Genetic
chemical_list: D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1