Mutation spectrum of the CYP1B1 gene in Indian primary congenital glaucoma patients.
OBJECTIVE
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.
Kallam Anji Reddy Molecular Genetics Laboratory, L.V. Prasad Eye Institute, Hyderabad, India.
Aramati Bindu Madhava
AB
Reddy
Kiranpreet
K
Kaur
Anil Kumar
AK
Mandal
Shirly George
SG
Panicker
Ravi
R
Thomas
Seyed Ehtesham
SE
Hasnain
Dorairajan
D
Balasubramanian
Subhabrata
S
Chakrabarti
D000293:Adolescent; D017668:Age of Onset; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D065633:Cytochrome P-450 CYP1B1; D004252:DNA Mutational Analysis; D016368:Frameshift Mutation; D005901:Glaucoma / Q000151:congenital* / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D007194:India; D007223:Infant; D007231:Infant, Newborn; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion
D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1