Identification of R368H as a predominant CYP1B1 allele causing primary congenital glaucoma in Indian patients.
OBJECTIVE
To investigate the predominant mutation in the CYP1B1 gene in patients in India with primary congenital glaucoma (PCG), using PCR-restriction fragment length polymorphism (RFLP) methods and to characterize the molecular defect in two generations of an affected family.


METHODS
DNA samples from 146 patients with PCG from 138 pedigrees were analyzed for several distinct mutations in CYP1B1 by PCR-RFLP.


RESULTS
PCR-RFLP screening revealed that 30.8% of patients were positive for any one of the six mutations (376insA, 528G-->A, 923C-->T, 959G-->A, 1449G-->A, and 1514C-->A), and 17.8% of the patients were found to have the rarely reported mutation R368H (1449G-->A). All mutations were confirmed by DNA sequencing.


CONCLUSIONS
The results suggest extensive allelic heterogeneity in the Indian patients with PCG, with the predominant allele being R368H among the 146 Indian patients tested. It appears possible to use this approach for carrier detection in pedigrees with a positive family history and in population screening. The approach also offers a method for rapid screening of potential carriers and affected individuals.
D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1; D004252:DNA Mutational Analysis; D005260:Female; D005901:Glaucoma / Q000151:congenital* / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D017422:Sequence Analysis, DNA
D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1