A novel frameshift founder mutation in the cytochrome P450 1B1 (CYP1B1) gene is associated with primary congenital glaucoma in Morocco

Clin Genet. 2002 Oct;62(4):334-9. doi: 10.1034/j.1399-0004.2002.620415.x.

Abstract

Primary congenital glaucoma (PCG) is a heterogeneous autosomal recessive disorder caused by unknown developmental defect(s) of the anterior chamber of the eye. A member of the cytochrome P450 gene family, CYP1B1, was found to be mutated in PCG patients in different populations, albeit to a variable extent. In this study, CYP1B1 mutations were searched for in 32 unrelated PCG patients from Morocco. Two mutations were detected in 11 (34%) patients. One, 4339delG, is novel and causes a frameshift at residue 179. The other, G61E, was previously found in patients from Turkey and Saudi Arabia. Seven patients were homozygous for 4339delG and two other patients for G61E, whereas the two remaining patients were compound heterozygotes. The close association of 4339delG with a rare allele of D2S177, a microsatellite marker located 270 kb upstream of CYP1B1, strongly suggested a founder effect for 4339delG. The occurrence of this mutation was tentatively dated at between 900 and 1700 years ago. Typing 4339delG and G61E mutations should help to prevent blindness resulting from a delayed diagnosis of PCG in Morocco.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Cytochrome P-450 CYP1B1
  • DNA Mutational Analysis
  • Exons
  • Founder Effect
  • Frameshift Mutation*
  • Genotype
  • Glaucoma / congenital
  • Glaucoma / genetics*
  • Humans
  • Microsatellite Repeats
  • Morocco
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length

Substances

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