Classification of posterior polymorphous corneal dystrophy as a corneal ectatic disorder following confirmation of associated significant corneal steepening.

Importance: The identification of steep corneal curvatures in a significant percentage of patients with posterior polymorphous corneal dystrophy (PPCD) confirms this previously reported association and suggests a role for the ZEB1 protein in keratocyte function.

Objective: To determine whether PPCD is characterized by significant corneal steepening.

Design, Setting, And Participants: Cross-sectional study at university-based and private ophthalmology practices of 38 individuals (27 affected and 11 unaffected) from 23 families with PPCD.

Analysis of the role of ZEB1 in the pathogenesis of posterior polymorphous corneal dystrophy.

Purpose: To determine how nonsense mutations in the transcription factor ZEB1 lead to the development of posterior polymorphous corneal dystrophy type 3 (PPCD3).

Methods: Whole-cell extracts were obtained from cultured human corneal epithelial cells (HCEpCs) as a source of ZEB1 protein. DNA-binding assays were performed using the whole-cell extract and oligonucleotide probes consisting of the two conserved E2-box motifs and surrounding nucleotides upstream of COL4A3.

The utility of next-generation sequencing in the evaluation of the posterior polymorphous corneal dystrophy 1 locus.

Purpose: To identify the genetic basis of posterior polymorphous corneal dystrophy 1 (PPCD1) using next-generation sequencing (NGS) of the common PPCD1 support interval, in which Sanger sequencing failed to identify a pathogenic mutation.

Methods: Enrichment of the portion of chromosome 20 containing the common PPCD1 interval was performed on DNA extracted from an affected and an unaffected member of a family previously linked to the PPCD1 locus. NGS using the Roche 454 Titanium platform was performed, followed by computational analysis using NextGENe Software.