Molecular analysis of CYP1B1 gene in patients affected by primary congenital glaucoma

Abstract

Abstract: : Purpose: Primary congenital glaucoma (PCG) is responsible for 0.01–0.04 % of blindness. Its prevalence at birth is 1/10000. Transmission mode is autosomic recessive with variable penetrance but recent studies stressed multifactorial and polygenic inheritance. Chromosomic anomalies are associated with PCG even if they are rarely accompanied by the classic form. Linkage studies identified a locus (GLC3A) in the 2p21 region, where the gene CYP1B1 associated with the most common form was found. A second locus was located in the 1p36 region (GLC3B) but the gene has not yet been identified. The proband's phenotype appears very early, with high IOP and progressive and aggressive clinical development. The goal of this study is to analyze the CYP1B1 gene in patients affected by PCG and in their families, in order to identify the hereditary forms and offer genetic counseling. Methods: A clinical form and genetic informed consent were required. DNA analysis was performed by PCR product direct sequencing. Results: We collected 29 patients from 21 families coming from different Italian regions. CYP1B1 molecular analysis allowed us to identify 8 published mutations (5 missense, one insertion, a deletion and a duplication) and 3 new mutations (two substitutions and a stop). Among the carrier patients 9 are double heterozygotes, one is homozygote and another has only a mutation. Analysis of five intragenic single nucleotide polymorphism proved 5'C–G–G–T–A 3' as the most common haplotype among Italian patients. Conclusions: CYP1B1 mutation frequency in affected patients (40%) emphasizes the hypothesis that other genes could be involved in this pathology and that the Italian mutation frequency is similar to the other EU studies.

Keywords: gene screening • intraocular pressure