PURPOSE: The human Cytochrome P450 gene CYP1B1 has been implicated in primary congenital glaucoma worldwide. The aim of this study was to understand the role of CYP1B1 mutations in causing primary congenital glaucoma in Indian populations. METHODS: The study included 64 new and unrelated cases of primary congenital glaucoma from different ethnic groups of India. Direct sequencing screened the coding and the promoter regions of CYP1B1. RESULTS: Sixteen pathogenic mutations were observed in 24 cases, of which 7 were novel. These included two frameshift mutations leading to deletions of 23 bp (g.3905del23bp) and 2 bp (g.7900-7901delCG) in exons II 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 binding cytochromes. Overall, CYP1B1 was involved in 37.50% (24/64) cases and homozygosity of the mutant allele was seen in 29.68% (19/64) and compound heterozygosity in 3.12% (2/64) of the cases, respectively. The frequency of CYP1B1 mutations was comparatively lower than Saudi Arabian, Slovakian Gypsys, and Turkish populations, largely due to genetic heterogeneity and ethnic diversities in Indian populations. Genotype-phenotype correlation indicated variable prognosis that could be due to the type of mutation, leading to alteration of CYP1B1 protein. CONCLUSIONS: This study provides a mutation spectrum of CYP1B1 causing primary congenital glaucoma in Indian populations that has implications in devising molecular diagnostics for rapid screening.
PURPOSE: The humanCytochrome P450 gene CYP1B1 has been implicated in primary congenital glaucoma worldwide. The aim of this study was to understand the role of CYP1B1 mutations in causing primary congenital glaucoma in Indian populations. METHODS: The study included 64 new and unrelated cases of primary congenital glaucoma from different ethnic groups of India. Direct sequencing screened the coding and the promoter regions of CYP1B1. RESULTS: Sixteen pathogenic mutations were observed in 24 cases, of which 7 were novel. These included two frameshift mutations leading to deletions of 23 bp (g.3905del23bp) and 2 bp (g.7900-7901delCG) in exons II 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 binding cytochromes. Overall, CYP1B1 was involved in 37.50% (24/64) cases and homozygosity of the mutant allele was seen in 29.68% (19/64) and compound heterozygosity in 3.12% (2/64) of the cases, respectively. The frequency of CYP1B1 mutations was comparatively lower than Saudi Arabian, Slovakian Gypsys, and Turkish populations, largely due to genetic heterogeneity and ethnic diversities in Indian populations. Genotype-phenotype correlation indicated variable prognosis that could be due to the type of mutation, leading to alteration of CYP1B1 protein. CONCLUSIONS: This study provides a mutation spectrum of CYP1B1 causing primary congenital glaucoma in Indian populations that has implications in devising molecular diagnostics for rapid screening.
Authors: Fereshteh Chitsazian; Betsabeh Khoramian Tusi; Elahe Elahi; Heidar Amini Saroei; Mohammad H Sanati; Shahin Yazdani; Mohammad Pakravan; Navid Nilforooshan; Yadollah Eslami; Mohammad Ali Zare Mehrjerdi; Reza Zareei; Mahmood Jabbarvand; Ali Abdolahi; Ali R Lasheyee; Arash Etemadi; Behnaz Bayat; Mehdi Sadeghi; Mohammad M Banoei; Behnam Ghafarzadeh; Mohammad R Rohani; Akram Rismanchian; Yvonne Thorstenson; Mansoor Sarfarazi Journal: J Mol Diagn Date: 2007-07 Impact factor: 5.568
Authors: Malkaram S Achary; Aramati B M Reddy; Subhabrata Chakrabarti; Shirly G Panicker; Anil K Mandal; Niyaz Ahmed; Dorairajan Balasubramanian; Seyed E Hasnain; Hampapathalu A Nagarajaram Journal: Biophys J Date: 2006-09-08 Impact factor: 4.033