Purpose: The purpose of this study was to characterize the five missense mutations in CYP1B1 gene identified in Pakistani families affected with primary congenital glaucoma (PCG) using various bioinformatics and protein modeling tools.
Methods: We previously reported four novel missense mutations in CYP1B1 gene segregating in consanguineous Pakistani families. These mutations were identified by direct sequencing of all coding exons, the exon-intron boundaries and the 5' untranslated region of CYP1B1 using genomic DNA from affected and unaffected family members. In order to understand the effect of CYP1B1 mutations on protein structure and function, we used bioinformatics tools to investigate five mutations including four novels (W434R, D374E, L487P and L177R) and one known (E229K) mutation previously reported by our group in four Pakistani PCG-affected families.
Results: In silico analysis of the missense mutations using the computational algorithms SNAP, I-Mutant 2.0 IUPred, PrDOS and PASTA predicted pathogenic effects on stability and function of protein.
Conclusion: In silico analysis of identified mutations confirmed their molecular pathogenicity. Similar analysis will be helpful in understanding of the biological role of CYP1B1 and the effect of mutations on the regulatory and enzymatic functions of CYP1B1 that result in PCG.
Keywords: Bioinformatics; CYP1B1; Missense mutation; Primary congenital glaucoma (PCG).