Mutation spectrum of the CYP1B1 gene in Indian primarycongenital glaucoma patients

[摘要] Purpose: The human Cytochrome P450 gene CYP1B1 has beenimplicated in primary congenital glaucoma worldwide. The aim of thisstudy was to understand the role of CYP1B1 mutations in causingprimary congenital glaucoma in Indian populations.Methods: The study included 64 new and unrelated cases of primarycongenital glaucoma from different ethnic groups of India. Directsequencing screened the coding and the promoter regions of CYP1B1.Results: Sixteen pathogenic mutations were observed in 24 cases, ofwhich 7 were novel. These included two frameshift mutations leading todeletions of 23 bp (g.3905del23bp) and 2 bp (g.7900-7901delCG) in exonsII and III, respectively. Four novel missense mutations viz. A115P,M132R, Q144P, S239R were noted in exon II, and one in exon III (G466D),whose residue is a part of the "signature sequence"(NH2-FXXGXXXCXG-COOH) and is present in all heme bindingcytochromes. Overall, CYP1B1 was involved in 37.50% (24/64) casesand homozygosity of the mutant allele was seen in 29.68% (19/64) andcompound heterozygosity in 3.12% (2/64) of the cases, respectively. Thefrequency of CYP1B1 mutations was comparatively lower than SaudiArabian, Slovakian Gypsys, and Turkish populations, largely due togenetic heterogeneity and ethnic diversities in Indian populations.Genotype-phenotype correlation indicated variable prognosis that couldbe due to the type of mutation, leading to alteration of CYP1B1protein.Conclusions: This study provides a mutation spectrum of CYP1B1causing primary congenital glaucoma in Indian populations that hasimplications in devising molecular diagnostics for rapid screening.

[学科分类] 生物化学/生物物理