Mutations in the CYP1B1 Gene Are an Uncommon Cause of Primary Congenital Glaucoma in Mexico

Abstract

Purpose:: The glaucomas are a heterogeneous group of diseases characterized by elevated intraocular pressure (IOP) that may lead to optic nerve damage and to progressive visual loss and blindness. Primary congenital glaucoma (PCG) is a severe form of glaucoma that manifests itself from birth to 3 years.When inherited, PCG is transmitted as an autosomal recessive trait. Three loci are associated with PCG: GLC3A (2p21), GLC3B(1p36), and GLC3C (14q24.3). GLC3A has been shown to be the gene for cytochrome P4501B1 or CYP1B1. Approximately 45 different mutations in the coding region of CYP1B1 have been reported in PCG families from different countries. This study investigated for the first time the prevalence of CYP1B1 mutations in PCG Mexican patients.

Methods:: 30 patients with PCG belonging to 30 different Mexican families were recruited from two National ophthalmologic centers. All subjects were clinically evaluated by at least one glaucoma specialist and diagnosed with PCG by slit lamp biomicroscopy, gonioscopy, and measurement of IOP. PCG was defined as an increase in IOP >21 mm Hg in both eyes before the age of three. Sporadic cases accounted for 90%. Consanguinity was proven in two familial cases. DNA was extracted from peripheral blood leukocytes and CYP1B1 coding region variants were characterized by PCR amplification and direct sequencing screening using a dye terminator method. DNA from parents of subjects with homozygous CYP1B1 mutations was also analyzed.

Results:: CYP1B1 analysis revealed that two unrelated PCG subjects had a homozygous E387K mutation. These patients pertained to familial cases with evidence of consanguinity. In the remaining 28 PCG patients, no pathogenic mutations were detected. Several polymorphisms were detected in the group, including R48G, A119S, V432L, and N453S.

Conclusions:: This is the first CYP1B1 analysis in Mexican subjects with PCG. Our results indicate that CYP1B1 mutations are not a common cause (<10%) of the disease in this ethnic group. The E387K mutation identified in two unrelated familial PCG cases has been described in Slovak and Brazilian populations. Our preliminary data indicate that the E387K could be a founder mutation in Mexican PCG patients.

Keywords: genetics • mutations • intraocular pressure