RESUMO
Background: Glaucoma is a neurodegenerative ophthalmic disorder and is considered among the leading causes of irreversible blindness. Primary open-angle glaucoma (POAG) is the most common type of glaucoma that affects after 30â¯years of life, progressing slowly, and manifests as decreased visual acuity leading to blindness if not treated. POAG is genetically heterogeneous, inherited most commonly in autosomal dominant mode. Several genes have been reported for POAG with myocilin (Myoc) being most common. The present study has been conducted to screen 25 POAG families with 2 or more affected members for their association with Myoc and CYP1B1 (the most common gene in primary congenital glaucoma). Methods: After approval from Institutional Ethical Review Committee (ERC), 25 POAG families were enrolled from the southern province (Sindh) of Pakistan. Written informed consent was obtained from all participating individuals and diagnosis was confirmed by consultant ophthalmologists using various instruments and means. Venous blood was obtained from affected individuals and their normal family members for DNA extraction and subsequent analysis. Results: All samples were initially screened for the Myoc gene followed by CYP1B1. Screening for Myoc revealed one previously reported variant c.144G>T in POAG-06 whereas screening for CYP1B1 in all 25 families showed a novel variant c.649G>A in POAG-02. The pathogenicity of the novel variant was confirmed using various bioinformatics tools. Conclusion: This is the first report of any POAG family found associated with a novel variant in CYP1B1 from the southern province of Pakistan whereas one family found associated with a reported variant in Myoc. The remaining 23 POAG families did not found to be associated with either Myoc or CYP1B1 indicating genetic heterogeneity of the population in this part of the world.
