CYP1B1 variants have low contribution to Pakistani patients with Primary Open Angle Glaucoma Page

Abstract Background Glaucoma is a group of complex neurodegenerative ophthalmological disorders and is the second common of cause of irreversible blindness around the globe. Primary open-angle glaucoma (POAG) is the commonest type of all glaucoma and is characterized by elevated intraocular pressure (IOP) leading to optic nerve damage and visual field defects. Inherited mutations in CYP1B1 are a rare cause of POAG. Objective This study was conducted to screen Pakistani population with POAG for CYP1B1 variants. Methods Detailed family history was recorded from all participating families. The disease was confirmed through ophthalmological examinations. Blood samples were collected for genomic DNA extraction. CYP1B1 exons were directly sequenced in one affected individual from each family. Results CYP1B1 sequencing revealed a novel heterozygous missense variant, c.649G>A (p.Asp217Asn). All affected individuals having the variant had characteristic glaucomatous changes with mean disease onset at 35 years. The unaffected individuals in the family had no signs of POAG. The prevalence of CYP1B1 associated POAG in study cohort is 4% (1/25). In silico predictions showed that p.Asp217Asn, substitution affects the structure and function of the protein. Conclusion The study suggests that CYP1B1 mutations are considered to have have less contribution in pathogenesis of POAG in Pakistani population studied. Identification of novel dominantly inherited variant shows allelic heterogeneity and may help in early diagnosis for effective management of the disease through genetic counseling.