A clinical and molecular genetic study of German patients with primary congenital glaucoma

Am J Ophthalmol. 2009 Apr;147(4):744-53. doi: 10.1016/j.ajo.2008.11.008. Epub 2009 Feb 4.

Abstract

Purpose: To estimate an accurate incidence rate for CYP1B1 mutations in German patients with primary congenital glaucoma (PCG).

Design: Observational case series.

Methods: Blood was obtained from 39 unrelated patients of German origin with clear clinical features of PCG and screened for mutations in the CYP1B1 gene using direct deoxyribonucleic acid sequencing. One hundred ethnically matched control subjects were screened for novel sequence variants using restriction fragment length polymorphism and denaturing high-performance liquid chromatography.

Results: Sequence analysis identified 11 different mutations in 7 patients (18%). Four patients were compound heterozygotes, 2 subjects heterozygous, and 1 homozygous for CYP1B1 mutations. One deletion (c.199_206del8) and 3 missense mutations (L177P, F190L, and S282N) were novel. None of the novel missense mutations identified was found in normal controls.

Conclusions: Our results indicate that only a minor proportion of German PCG patients harbor mutations in the CYP1B1 gene and are in line with similar studies from other ethnic populations in which the rate of consanguinity is low. In addition, this is the first report discussing the phenotypes of German PCG patients with and without CYP1B1 mutations.

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Aryl Hydrocarbon Hydroxylases
  • Chromatography, High Pressure Liquid
  • Cytochrome P-450 CYP1B1
  • Cytochrome P-450 Enzyme System / genetics*
  • DNA Mutational Analysis
  • Female
  • Germany
  • Glaucoma / congenital
  • Glaucoma / genetics*
  • Humans
  • Incidence
  • Male
  • Molecular Biology
  • Molecular Sequence Data
  • Mutation*
  • Phenotype
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide
  • Sequence Analysis, DNA
  • White People / genetics

Substances

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