No Pathogenic Mutations Identified in the COL8A2 Gene or Four Positional Candidate Genes in Patients with Posterior Polymorphous Corneal Dystrophy

PURPOSE. To identify the genetic basis of posterior polymorphous corneal dystrophy (PPCD) through screening of four positional candidate genes and the COL8A2 gene, in which a presumed pathogenic mutation has previously been identified in affected patients. METHODS. DNA extraction, PCR amplification, and direct sequencing of the COL8A2, BFSP1, CST3, MMP9, and SLPI genes were performed in 14 unrelated, affected patients and in unaffected family members. RESULTS. In the COL8A2 gene, the previously identified, presumed pathogenic mutation (Gln455Lys) was not discovered in any of the affected patients. A missense mutation, Thr502Met, was identified in 2 of the 14 affected probands, although it was not considered to be pathogenic, as it has been identified in unaffected individuals. Although several novel and previously identified single nucleotide polymorphisms producing synonymous and missense amino acid substitutions were identified in the COL8A2, BFSP1, CST3, MMP9, and SLPI genes, no presumed pathogenic sequence variants were found. CONCLUSIONS. No pathogenic mutations were identified in the COL8A2 gene or in several positional candidate genes in a series of patients with PPCD, indicating that other genetic factors are involved in the development of this autosomal dominant corneal dystrophy. (Invest Ophthalmol Vis Sci

Analysis of the Role of ZEB1 in the Pathogenesis of Posterior Polymorphous Corneal Dystrophy

ZEB1-mediated alterations in COL4A3 expression are most likely associated with the pathogenesis of posterior polymorphous corneal dystrophy type 3 (PPCD3), although the demonstration of COL4A3 expression in healthy adult human corneal endothelial cells (HCEnCs) indicates that PPCD3 is not caused simply by the ectopic expression of COL4A3