Molecular Analysis of the CYP1B1 gene in Congenital Glaucoma Brazilian Patients

Abstract

Purpose: : Primary congenital glaucoma (PCG) is a severe form of glaucoma, which has its onset from neonatal period to three years of age. When hereditary it is transmitted as an autosomal recessive trait with variable penetrance. Three loci have been described, but only one gene was identified, CYP1B1, located in the GLC3A locus, on chromosome 2p21. The aim of this study was to screen PCG Brazilian patients and their parents for mutations in the CYP1B1 gene.

Methods: : Thirty three PCG patients from 30 different families were evaluated through direct sequencing of the CYP1B1 gene coding regions and intron/exon boundaries.

Results: : Mutations were detected in 9 of 30 unrelated patients, a prevalence of 30%. Ten different mutations were observed, three of which, to our knowledge, are being reported for the first time. A deletion at exon 2, 4635delT, that leads to a stop codon at aminoacid 277 was observed in two unrelated patients. In three brothers (two twins), two other new alterations were described in heterozygosity, 4523delC in exon 2, leading to a stop codon at aminoacid 243 and a T to A point mutation in exon 3, at position 7970, changing a leucine for a glutamin (L378Q). Four patients were compound heterozygous, 2 were homozygous and in three only one mutation was detected. The previously reported polymorphisms 3793T to C, R48G, A119S, L432V, D449D and N453S were also identified in our patients.

Conclusions: : This work reports a 30% prevalence of CYP1B1 mutations in PCG Brazilian patients, describing three new different alterations related to the disease. Taken together, the two studies involving Brazilian patients reflect the genetic heterogeneity of the disease in this population and open possibilities to further analysis in other candidate loci.

Keywords: gene screening • genetics • optic nerve