CYP1B1 gene analysis in primary congenital glaucoma Brazilian patients: novel mutations and association with poor prognosis.
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.
Della Paolera
Maurício
M
Department of Ophthalmology, Glaucoma Service, Faculty of Medical Sciences, Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brazil.
de Vasconcellos
José Paulo Cabral
JP
Umbelino
Cristiano Caixeta
CC
Kasahara
Niro
N
Rocha
Mylene Neves
MN
Richeti
Flávio
F
Costa
Vital Paulino
VP
Tavares
Anderson
A
de Melo
Mônica Barbosa
MB
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
D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1