Mutational analysis of CYP1B1 gene in Pakistani pediatric patients affected with Primary Congenital Glaucoma

Background: Glaucoma is the significant cause of blindness all over the world. Primary congenital glaucoma (PCG) reduces the vision and ultimately causes the blindness by damaging the aqueous drainage system of the eye. The purpose of the current study was to determine the pathogenic mutations in the CYP1B1 gene responsible for PCG.Methods: A total of thirty-five PCG patients were enrolled in this study. Blood samples were collected from the enrolled patients, and after DNA extraction and amplification, the coding regions of CYP1B1 were sequenced to determine the pathogenic mutations. In-silico analysis of the identified mutation was executed to study the effect of genetic variation on protein structure.Results: One mutation, c.1169 G>A has been revealed in exon 3 of the CYP1B1 gene leading to p.R390H, present in 20% of the patients enrolled. Besides, two missense sequence variants c.1294G>C (2 patients), c.1358A>G (4 patients) and a synonymous variant c.1347T>C (18 patients) has also been observed.Conclusion: Our study not only reaffirms the role of CYP1B1 mutations in PCG but also supports the use of genetic screening for molecular diagnosis and carrier identification, which will reduce the burden of disease on society. Furthermore, the in-silico analysis of the identified mutations provided an in-depth understanding of the PCG pathogenesis at the molecular level.Keywords: Primary congenital glaucoma; CYP1B1, mutation; Genetic variatio