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

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.

Whole-Exome Sequencing of 24 Spanish Families: Candidate Genes for Non-Syndromic Pediatric Keratoconus

“…Finally, the presence of a missense variant in heterozygosis in the DUXA gene associated with corneal dystrophies such as PPCD p.(Pro40Ser) stands out for its role in development [32]. There are several case reports where variants in genes that produce PPCD have also been detected in patients with keratoconus [53]. Therefore, the DUXA gene is proposed as a candidate in the pathology study.…”

“…Thus, articles link ZEB1 to keratoconus. Heterozygous mutations have been found in patients with FECD or PPCD and KC and in probands with KC [53,55].…”