title: Molecular genetics of primary congenital glaucoma in Brazil.
abstract: OBJECTIVE
  To determine the distribution of CYP1B1 gene mutations in Brazilian patients with primary congenital glaucoma (PCG).
  
  
  METHODS
  PCG diagnosis was established by presence of buphthalmos in at least one affected eye and associated high intraocular pressures before the age of 3 years. CYP1B1 mutation screening of 52 patients with PCG was performed by SSCP and direct sequencing of PCR fragments.
  
  
  RESULTS
  Eleven mutations, four of which are novel, were observed in 26 (50%) individuals. A new frameshift mutation (4340delG) was observed in 20.2% of all individuals screened. These individuals had early-onset, bilateral glaucoma that necessitated multiple surgical interventions. CYP1B1 mutations were twice as frequent in affected individuals of European descent as in individuals of African descent. Analysis of six intragenic single nucleotide polymorphisms (SNPs) established 5'-C-C-G-G-T-A-3' as the most common haplotype among the affected Brazilian individuals. A nonsense mutation (W57X) previously reported in an individual with Peters anomaly (compound heterozygote) was also observed in two individuals with PCG but combined with different mutations. A newly developed SSCP assay enabled us to detect all DNA mutations and polymorphisms previously detected by direct sequencing.
  
  
  CONCLUSIONS
  Our results indicate that CYP1B1 mutations may be responsible for half of cases of PCG in the Brazilian population. The SNP haplotype 5'-C-C-G-G-T-A-3' was associated with the majority of CYP1B1 mutations. This haplotype harbors the high-activity V432 allele, which is emerging as a putative susceptibility factor in several cancers.
authors.affiliation: Molecular Ophthalmic Genetics Laboratory, Surgical Research Center, Department of Surgery, University of Connecticut Health Center, Farmington, Connecticut CT 06030-1110, USA.
authors.forename: Ivaylo R
authors.initials: IR
authors.lastname: Stoilov
authors.forename: Vital P
authors.initials: VP
authors.lastname: Costa
authors.forename: Jose P C
authors.initials: JP
authors.lastname: Vasconcellos
authors.forename: Monica B
authors.initials: MB
authors.lastname: Melo
authors.forename: Alberto J
authors.initials: AJ
authors.lastname: Betinjane
authors.forename: Jose C E
authors.initials: JC
authors.lastname: Carani
authors.forename: Ernst V
authors.initials: EV
authors.lastname: Oltrogge
authors.forename: Mansoor
authors.initials: M
authors.lastname: Sarfarazi
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases; D001938:Brazil; D002675:Child, Preschool; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D005901:Glaucoma / Q000151:congenital* / Q000201:enzymology* / Q000208:ethnology; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007429:Intraocular Pressure; D008967:Molecular Biology; D009154:Mutation; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D014792:Visual Acuity
chemical_list: D017931:DNA Primers; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1