SUMMARY
Objective: To identify the genetic variants in the CYP1B1 gene associated with Primary Congenital Glaucoma (PCG) and to predict its pathological effect.Method: A descriptive study was conducted in the time period of nine months (September 2021-May 2022) after the ethical approval was taken from The Children Hospital and Institute of Child Health (CH & ICH). Two milliliters of the blood sample from PCG-affected individuals were collected in EDTA vacutainers and genomic DNA was extracted by a phenol-chloroform method. The semi-quantification of extracted DNA was done by agarose gel electrophoresis. PCR amplification was performed by specific primers of CYP1B1 gene then termination sequencing (di-deoxy) was done to detect the genetic variants. Different bioinformatics tools such as BLAST, Ensembl, Clustal Omega, Polyphen and SIFT were used for the further analysis of mutation causing the disease.Results: A total of 85% of patients were bilaterally affected, while 15% were unilaterally affected. Mutation analysis identified five non related known variants. Two missense mutations (c.355 G/T p.A119S and c.685G/A p.E229K) occurred in 94% patients and intragenic SNP occurred in 29% patients along with the 1% somatic (c.693C/A p.F231L) and stop gained mutation (c.840C/A p.C280*).Conclusion: Genetic analysis in the current study showed that 85% of PCG affected patients were due to the CYP1B1 mutation, and disease heterogeneity might be reduced through genetic counseling.doi: https://doi.org/10.12669/pjms.39.2.7081How to cite this: Zahid T, Khan MU, Zulfiqar A, Jawad F, Saleem A, Khan AR. Investigation of mutational spectrum in cytochrome P4501B1 (CYP1B1) as the principal cause of primary congenital glaucoma. Pak J Med Sci. 2023;39(2):---------. doi: https://doi.org/10.12669/pjms.39.2.7081This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.