Identification of R368H as a predominant CYP1B1 allele causing primary congenital glaucoma in Indian patients

Invest Ophthalmol Vis Sci. 2003 Oct;44(10):4200-3. doi: 10.1167/iovs.02-0945.

Abstract

Purpose: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • Cytochrome P-450 CYP1B1
  • DNA Mutational Analysis
  • Female
  • Glaucoma / congenital*
  • Glaucoma / enzymology
  • Glaucoma / ethnology
  • Glaucoma / genetics*
  • Humans
  • India / epidemiology
  • Male
  • Mutation*
  • Pedigree
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Sequence Analysis, DNA

Substances

  • Aryl Hydrocarbon Hydroxylases
  • CYP1B1 protein, human
  • Cytochrome P-450 CYP1B1