Posterior Polymorphous Corneal Dystrophy in a Patient with a Novel ZEB1 Gene Mutation

Int J Mol Sci. 2022 Dec 22;24(1):209. doi: 10.3390/ijms24010209.

Abstract

Posterior polymorphous corneal dystrophy (PPCD), a rare, bilateral, autosomal-dominant, inherited corneal dystrophy, affects the Descemet membrane and corneal endothelium. We describe an unusual presentation of PPCD associated with a previously unknown genetic alteration in the ZEB1 gene. The proband is a 64-year-old woman diagnosed with keratoconus referred for a corneal endothelium study who presented endothelial lesions in both eyes suggestive of PPCD, corectopia and iridocorneal endothelial synechiae in the right eye and intrastromal segments in the left eye. The endothelial count was 825 in the right eye and 1361 in the left eye, with typical PPCD lesions visible under specular and confocal microscopy. In the next generation sequencing genetic analysis, a heterozygous c.1A > C (p.Met1Leu) mutation was found in the ZEB1 gene (TCF8). The PPCD3 subtype is associated with corneal ectasia, and both can appear due to a pathogenic mutation in the ZEB1 gene (OMIM #189909). However, our patient had a previously unreported mutation in the ZEB1 gene, which mediates the transition between cell lines and provides a pathogenic explanation for the epithelialisation of the corneal endothelium, a characteristic of PPCD.

Keywords: ZEB1; confocal microscopy; iridocorneal endothelial syndrome; keratoconus; posterior polymorphous corneal dystrophy.

Publication types

  • Case Reports

MeSH terms

  • Corneal Dystrophies, Hereditary* / genetics
  • Corneal Dystrophies, Hereditary* / pathology
  • Endothelium, Corneal / metabolism
  • Female
  • Homeodomain Proteins* / genetics
  • Homeodomain Proteins* / metabolism
  • Humans
  • Middle Aged
  • Mutation
  • Transcription Factors / metabolism
  • Zinc Finger E-box-Binding Homeobox 1 / genetics
  • Zinc Finger E-box-Binding Homeobox 1 / metabolism

Substances

  • Homeodomain Proteins
  • Transcription Factors
  • Zinc Finger E-box-Binding Homeobox 1
  • ZEB1 protein, human

Supplementary concepts

  • Corneal Dystrophy, Posterior Polymorphous, 1