Molecular and clinical evaluation of primary congenital glaucoma in Kuwait

Am J Ophthalmol. 2006 Mar;141(3):512-6. doi: 10.1016/j.ajo.2005.11.001.

Abstract

Purpose: To report the spectrum of the CYP1B1 mutation in Kuwaiti patients with primary congenital glaucoma (PCG).

Design: Clinical diagnosis of PCG and laboratory based experimental study.

Methods: Polymerase chain reaction-restriction polymorphism length fragment (PCR-RPLF) and direct sequencing of exon 2 and the coding region of exon 3 of CYP1B1 gene were the methods used for screening 17 PCG patients, their families, and 105 health individuals from the same ethnicity.

Results: Four different mutations were detected in CYP1B1 in 70.6% of the screened patients. The most common one (47%) was homozygote Gly61Glu mutation, previously described in Saudi Arabia, Turkey, and Morocco; all patients were products of consanguineous marriages. The second common mutation was a novel missense (Ala388Thr) mutation found in three patients (17.6%) as compound heterozygote with Arg368His in one patient, and with Gly61Glu in another one while the second mutation in third patient was not detected in the CYP1B1 gene. One patient (5.8%) was homozygote for Cyt280X mutation previously reported in only one Japanese family. In addition to these mutations, a novel Val422Gly polymorphic site was found in three of the PCG patients and in 18 of the 210 tested chromosomes of healthy volunteers.

Conclusions: The CYP1B1 mutation spectrum of Kuwaiti PCG patients is similar to that detected in the neighboring countries. No clear genotype-phenotype correlation detected in patients showed different types of CYP1B1 mutation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aryl Hydrocarbon Hydroxylases
  • Child, Preschool
  • Consanguinity
  • Cytochrome P-450 CYP1B1
  • Cytochrome P-450 Enzyme System / genetics*
  • DNA Mutational Analysis
  • Exons / genetics
  • Genetic Testing
  • Glaucoma / congenital*
  • Glaucoma / ethnology
  • Glaucoma / genetics*
  • Humans
  • Infant
  • Infant, Newborn
  • Intraocular Pressure
  • Kuwait / epidemiology
  • Mutation*
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Sequence Analysis, DNA

Substances

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