Genotype-phenotype analysis of Bietti crystalline dystrophy in a family with the CYP4V2 Ile111Thr mutation

Cornea. 2013 Jul;32(7):1002-8. doi: 10.1097/ICO.0b013e31828a27bc.

Abstract

Purpose: The purposes of this study were to evaluate the genotypic and phenotypic correlations of Bietti crystalline dystrophy and to investigate the utility of in vivo corneal confocal microscopy in diagnosing this disorder.

Methods: A Spanish woman (proband) with a clinical diagnosis of Bietti crystalline dystrophy and 7 members of her family were recruited prospectively for complete clinical ophthalmic examination and genetic study. The medical records of an additional family member were reviewed retrospectively. Genomic DNA was obtained from blood samples, and 11 exons of the CYP4V2 gene were screened for mutations by polymerase chain reaction DNA sequencing.

Results: Clinical examination revealed an atypical pattern of corneal dystrophy with central and paracentral distribution not only in the proband but also in 2 elderly heterozygous carriers. Corneal deposits were observed by slit-lamp examination and in vivo corneal confocal microscopy. Genetic analysis revealed the homozygous CYP4V2 Ile111Thr mutation in the proband and identified 5 heterozygous carriers.

Conclusions: The authors identified a case of Bietti crystalline dystrophy with central and paracentral keratopathy and the molecular analysis of the causative gene in a Spanish family. Data suggest a dose-dependent phenotype ranging from subclinical corneal changes in subjects carrying 1 mutant Ile111Thr CYP4V2 allele to the complete manifestation of the disease in homozygous subjects. In vivo corneal confocal microscopy is a useful technique in the diagnosis of this disorder.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Corneal Dystrophies, Hereditary / diagnosis*
  • Corneal Dystrophies, Hereditary / genetics*
  • Cytochrome P-450 Enzyme System / genetics*
  • Cytochrome P450 Family 4
  • Electroretinography
  • Exons / genetics
  • Female
  • Genetic Association Studies
  • Heterozygote
  • Humans
  • Male
  • Microscopy, Confocal
  • Middle Aged
  • Pedigree
  • Point Mutation*
  • Polymerase Chain Reaction
  • Prospective Studies
  • Retinal Diseases / diagnosis*
  • Retinal Diseases / genetics*
  • Tomography, Optical Coherence
  • Visual Acuity

Substances

  • Cytochrome P-450 Enzyme System
  • CYP4V2 protein, human
  • Cytochrome P450 Family 4

Supplementary concepts

  • Bietti Crystalline Dystrophy