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Primary role of CYP1B1 in Indian juvenile-onset POAG patients

Moulinath Acharya1, Suddhasil Mookherjee, Ashima Bhattacharjee

  • 1Human Genetics & Genomics Division, Indian Institute of Chemical Biology, Kolkata, India.

Molecular Vision
|May 12, 2006
PubMed

Insights

Mutations in the CYP1B1 gene were identified in some primary open-angle glaucoma (POAG) patients, suggesting it may rarely cause juvenile onset POAG (JOAG) through monogenic inheritance. Screening for CYP1B1 mutations is important in JOAG patients lacking other known mutations.

Area of Science:

  • Genetics
  • Ophthalmology
  • Molecular Biology

Background:

  • The cytochrome P450 superfamily enzyme, CYP1B1, is linked to primary congenital glaucoma (PCG).
  • Emerging evidence suggests CYP1B1 may act as a modifier locus in primary open-angle glaucoma (POAG).

Purpose of the Study:

  • To investigate the potential role of CYP1B1 in POAG patients.
  • To identify allelic variants in CYP1B1 associated with POAG.

Main Methods:

  • Genomic DNA from 200 Indian POAG patients and 100 controls was analyzed.
  • The coding sequence of CYP1B1 was amplified using PCR and subjected to direct DNA sequencing.

Main Results:

  • Six mutations in CYP1B1 were found in nine POAG patients, with no mutations detected in controls.
  • One novel homozygous mutation (R523T) and five heterozygous mutations (three reported, two novel) were identified.
  • A homozygous mutation in a familial juvenile onset POAG case cosegregated with the disease, indicating autosomal recessive inheritance. Novel mutations were in a region distinct from PCG-associated mutations.
  • Single nucleotide polymorphisms (SNPs) in CYP1B1 were observed in both POAG patients and controls.

Conclusions:

  • CYP1B1 mutations can rarely be the primary cause of juvenile onset POAG (JOAG) via monogenic association.
  • Genetic screening of CYP1B1 is recommended for JOAG patients negative for mutations in previously identified POAG candidate genes.
Abstract

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