Mutations in CYP1B1, the gene for cytochrome P4501B1, are the predominant cause of primary congenital glaucoma in Saudi Arabia

Am J Hum Genet. 1998 Feb;62(2):325-33. doi: 10.1086/301725.


The autosomal recessive disorder primary congenital glaucoma (PCG) is caused by unknown developmental defect(s) of the trabecular meshwork and anterior chamber angle of the eye. Homozygosity mapping with a DNA pooling strategy in three large consanguineous Saudi PCG families identified the GLC3A locus on chromosome 2p21 in a region tightly linked to PCG in another population. Formal linkage analysis in 25 Saudi PCG families confirmed both significant linkage to polymorphic markers in this region and incomplete penetrance, but it showed no evidence of genetic heterogeneity. For these 25 families, the maximum combined two-point LOD score was 15.76 at a recombination fraction of .021, with the polymorphic marker D2S177. Both haplotype analysis and homozygosity mapping in these families localized GLC3A to a 5-cM critical interval delineated by markers D2S2186 and D2S1356. Sequence analysis of the coding exons for cytochrome P4501B1 (CYP1B1) in these 25 families revealed three distinctive mutations that segregate with the phenotype in 24 families. Additional clinical and molecular data on some mildly affected relatives showed variable expressivity of PCG in this population. These results should stimulate a study of the genetic and environmental events that modify the effects of CYP1B1 mutations in ocular development. Furthermore, the small number of PCG mutations identified in this Saudi population makes both neonatal and population screening attractive public health measures.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aryl Hydrocarbon Hydroxylases*
  • Base Sequence
  • Chromosome Mapping
  • Chromosomes, Human, Pair 2*
  • Cytochrome P-450 CYP1B1
  • Cytochrome P-450 Enzyme System / genetics*
  • Exons
  • Family
  • Female
  • Genetic Linkage
  • Genetic Markers
  • Glaucoma / congenital*
  • Glaucoma / enzymology
  • Glaucoma / genetics*
  • Homozygote
  • Humans
  • Male
  • Pedigree
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Saudi Arabia
  • Trabecular Meshwork / pathology


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