| Subtype / OMIM disease ID | Gene (OMIM gene ID) | Variant types / hotspots (example) | Molecular mechanism | Key clinical features / complications | Key supporting citations |
|---|---|---|---|---|---|
| **PPCD1** / **OMIM 122000** | **OVOL2** (**OMIM 616441**) | Non-coding **promoter** variants in a conserved proximal promoter region; examples: **c.-307T>C**, **c.-274T>G**, **c.-370T>C**; related severe allelic CHED1 family with **c.-339_361dup** | Promoter variants increase OVOL2 transcriptional activity, causing **ectopic/increased OVOL2 expression** in corneal endothelium; OVOL2 is a MET-promoting transcription factor that **represses ZEB1**, driving endothelial cell-state transition toward epithelial-like phenotype | Typical PPCD posterior corneal lesions (vesicles/bands/gray-white opacities), endothelial dysfunction, corneal edema/haze, iris abnormalities/adhesions, secondary glaucoma risk; **~20–25%** of affected individuals may require corneal transplantation in PPCD overall; in OVOL2-linked families, **~30% secondary glaucoma** and about **one-third underwent keratoplasty**; severe early-onset/founder families may present from infancy and need repeated grafting. Czech prevalence estimate for PPCD overall: **~1 per 80,000** | (pqac-00000021, pqac-00000022, pqac-00000024, pqac-00000026, pqac-00000044) |
| **PPCD3** / **OMIM 609141** | **ZEB1** (**OMIM 189909**) | Predominantly heterozygous **loss-of-function** variants: nonsense, frameshift, splice, whole-gene/partial deletions; example: **c.1279C>T p.Glu427\***; rare missense variants also reported in some families | **ZEB1 haploinsufficiency** causes a MET-like **endothelial-to-epithelial transition (EnET)** with a **cadherin switch** (↓CDH2, ↑CDH1), epithelial-like transcriptome, altered adhesion/proliferation/migration, and endothelial stratification | Bilateral often asymmetric PPCD lesions, reduced endothelial cell density, occasional corectopia/iridocorneal synechiae, association with corneal steepening/ectasia in some cases; PPCD3 is often milder than OVOL2-linked disease but variable. Familial studies suggest **~95% penetrance**, yet documented **non-penetrance** exists, so true penetrance may be lower. ZEB1 LoF alleles are extremely rare in population databases | (pqac-00000036, pqac-00000037, pqac-00000038, pqac-00000047, pqac-00000050) |
| **PPCD4** / **OMIM 618031** | **GRHL2** (**OMIM 608576**) | Non-coding **regulatory / intron 1** variants; examples: **c.20+544G>T**, **c.20+257delT**, **c.20+133delA** | Regulatory variants increase GRHL2 transcription, causing **ectopic GRHL2 expression** in corneal endothelium; GRHL2 promotes epithelial identity and represses/acts upstream of **ZEB1**, producing MET-like transition with epithelial markers (e.g., E-cadherin, CK7) | Typical PPCD lesions with irregular posterior corneal surface, endothelial multilayering, corneal edema (including infantile onset in some), reduced endothelial cell density, corectopia/band keratopathy; in the large Czech series with recurrent variant, **25.9% underwent corneal transplantation** and **25.9% developed glaucoma**; mean first keratoplasty ~35 years, mean glaucoma diagnosis ~46 years | (pqac-00000029, pqac-00000030, pqac-00000033, pqac-00000034, pqac-00000044) |


*Table: This table summarizes the main genetically supported PPCD subtypes—OVOL2/PPCD1, ZEB1/PPCD3, and GRHL2/PPCD4—covering variant classes, mechanisms, clinical complications, and the strongest available evidence. It is useful for quickly comparing subtype-specific diagnostic and counseling implications.*