Name of the disease (synonyms) CUGC for posterior polymorphous corneal dystrophy (PPCD).OMIM# of the disease 122000; 609141; 618031.Name of the analysed genes or DNA/chromosome segments OVOL2 (PPCD1); ZEB1 (PPCD3); GRHL2 (PPCD4).OMIM# of the gene(s) 616441; 189909; 608576. Review of the analytical and clinical validity as well as of the clinical utility of DNA-based testing for variants in theOVOL2, ZEB1andGRHL2gene(s) in a diagnostic setting, predictive and parental settings and for risk assesment in relatives.
Alterations in GRHL2-OVOL2-ZEB1 axis and aberrant activation of Wnt signaling lead to altered gene transcription in posterior polymorphous corneal dystrophy.
Absence of the PPCD1 phenotype in animals haploinsufficient for Csrp2bp or both Csrp2bp and Dzank1 rules out haploinsufficiency of these genes as a cause of mouse PPCD1.
On review of almost all of the published cases, the description appeared most similar to a type of posterior polymorphous corneal dystrophy linked to the same chromosome 20 locus (PPCD1).
We have termed this the "mouse PPCD1" phenotype and mapped the mouse locus for this phenotype, designated "Ppcd1", to a 6.1 Mbp interval on Chromosome 2, which is syntenic to the human Chromosome 20 PPCD1 interval.
Multiple relatives were affected with PPMD with apparent autosomal dominant inheritance, but surprisingly, the PPMD, congenital hereditary endothelial dystrophy 1 (CHED1) and CHED2 loci on chromosome 20 and the collagen, type VIII, alpha-2 (COL8A2) gene were excluded by linkage and haplotype analyses.