title: CYP1B1 gene analysis in primary congenital glaucoma Brazilian patients: novel mutations and association with poor prognosis.
abstract: OBJECTIVE
  To determine the spectrum of CYP1B1 gene mutations in Brazilian patients with primary congenital glaucoma, and to correlate the presence of alterations in the CYP1B1 gene sequence with clinical aspects of the disease.
  
  
  METHODS
  Thirty nonrelated patients with primary congenital glaucoma were studied. Molecular analysis consisted of the codifying region sequencing (exons 2 and 3) and intron/exon boundaries.
  
  
  RESULTS
  CYP1B1 gene mutations were present in 9 (30%) of the 30 patients. The structural changes in the CYP1B1 gene previously described in the literature and observed in our study were Q19X, P437L, A443G, g.4340delG, g.7901_79013delGAGTGCAGGCAGA, g.8182delG, and g.8214_8215delG. Three new mutations were observed: 4635delT, 4523delC, and L378Q, in addition to 3793T→C, R48G, A119S, L432V, D449D, and N453S polymorphisms. Patients carrying CYP1B1 gene mutations needed more surgical procedures to control intraocular pressure, either when both eyes were evaluated (P=0.003) or when the worst eye of the patient was analyzed (P=0.011). In relation to the number of affected eyes, all patients with mutations (n=9/9) developed bilateral glaucoma, whereas 11/21 patients without mutations in the CYP1B1 gene had bilateral glaucoma (P=0.013).
  
  
  CONCLUSIONS
  In this group of primary congenital glaucoma patients, a 30% mutation frequency in the CYP1B1 gene was observed. The presence of mutations was associated with a more severe form of the disease, requiring more surgeries for intraocular pressure control and with a higher rate of bilateral cases.
authors.affiliation: Department of Ophthalmology, Glaucoma Service, Faculty of Medical Sciences, Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brazil.
authors.forename: Maurício
authors.initials: M
authors.lastname: Della Paolera
authors.forename: José Paulo Cabral
authors.initials: JP
authors.lastname: de Vasconcellos
authors.forename: Cristiano Caixeta
authors.initials: CC
authors.lastname: Umbelino
authors.forename: Niro
authors.initials: N
authors.lastname: Kasahara
authors.forename: Mylene Neves
authors.initials: MN
authors.lastname: Rocha
authors.forename: Flávio
authors.initials: F
authors.lastname: Richeti
authors.forename: Vital Paulino
authors.initials: VP
authors.lastname: Costa
authors.forename: Anderson
authors.initials: A
authors.lastname: Tavares
authors.forename: Mônica Barbosa
authors.initials: MB
authors.lastname: de Melo
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases; D001483:Base Sequence; D001938:Brazil; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D006871:Hydrophthalmos / Q000235:genetics* / Q000601:surgery; D007223:Infant; D007429:Intraocular Pressure; D007438:Introns / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis
chemical_list: D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1