Investigation of CYP1B1 mutations in Chinese patients with primary congenital glaucoma

Mol Vis. 2009:15:432-7. Epub 2009 Feb 27.

Abstract

Purpose: This study was conducted to investigate the mutation spectrum of the cytochrome P450 gene (CYP1B1) in Chinese patients with primary congenital glaucoma (PCG).

Methods: The coding regions of CYP1B1 from 41 Chinese PCG patients were analyzed using polymerase chain reaction (PCR) and heteroduplex analysis-single strand conformation polymorphism (HA-SSCP) followed by subsequent cloning and bidirectional sequencing. New variants were confirmed by restriction fragment length polymorphism (RFLP) analysis in 80 normal Chinese controls.

Results: Six distinct mutations, four of which are novel, were identified in 14.6% (6/41) of all patients. The CYP1B1 mutations in two patients were homozygous, and the other four patients were compound heterozygous. Beyond the four novel mutations (g.4531_4552del22bp, g.4633delC, p.S336Y, and p.I471S), two reported missense mutations (R469W and R390H) were also identified. The missense mutation, R390H, was involved in 9.8% (4/41) of patients in our study. None of the novel mutations was observed in any of the 80 controls.

Conclusions: Our results support the premise that CYP1B1 is a major gene for PCG, appearing to be responsible for the disease in roughly one in six Chinese PCG patients. The R390H mutation was identified as a predominant CYP1B1 allele among the Chinese PCG patients in our study. This observation emphasizes the importance of mutational screening of CYP1B1, especially for the R390H mutation in Chinese patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Arginine
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Asian People / genetics*
  • Child, Preschool
  • Cytochrome P-450 CYP1B1
  • Female
  • Glaucoma / congenital*
  • Glaucoma / genetics*
  • Heterozygote
  • Histidine
  • Homozygote
  • Humans
  • Infant
  • Male
  • Mutation*
  • Mutation, Missense
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single-Stranded Conformational
  • Young Adult

Substances

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