摘要：Primary congenital glaucoma (PCG) is a rare form of autosomal recessive disorder which shows its symptoms during early infantile period. These symptoms may include enlargement of globe, reduced visual acuity, blepharospasm, edema, photophobia and corneal opacification. CYP1B1 (cytochrome P4501B1) gene sited at locus GLC3A is considered as most common mutated gene in PCG patients. Frequency of disease causing CYP1B1 mutations differs among different populations ranging from less than 10% to 100%. There is a great diversity of mutations of CYP1B1 gene studied in the PCG pathogenesis worldwide. In this study, blood samples of both diseased and healthy individuals of 6 Pakistani families affected with PCG, were collected mutation analysis of CYP1BSanger sequencing of exons of CYP1B1 gene identify potentially pathogenic variants in these families. The identified variants were solved with one novel mutation (c.1551_1551delA), chr2:38297946_38297946delT, one known (c.1347T>C), chr2:38298150A>G, rs1056837 and homozygous nonsynonymous SNP (c.406C>A) in were found in two of the families respectively. Another known polymorphism (c.1294G>C) chr2:38298203C>G was observed in one of our patient, resulting in protein change V432L, signifying its role in disease pathogenesis. Additionally two more novel polymorphisms are found in two of our families i.e. cDNA.2218A>C, chr2:38297681T>G with no effect at protein level, and cDNA.2215G>T, chr2:38297684C>A, further analyses failed to indicate the pathogenic nature of these variants and majority of these were also present in public databases. The identification of CYP1B1 mutations in 33% families (2 out of 6) in this study indicates that mutations in this gene are the major cause of PCG in Pakistan as well. Additional work is required to identify the underlying mutations in the remaining four families..
