ORPHA: 98973; DO: 0110856;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 1p34.3 | Corneal dystrophy, posterior polymorphous 2 | 609140 | Autosomal dominant | 3 | COL8A2 | 120252 |
A number sign (#) is used with this entry because of evidence that posterior polymorphous corneal dystrophy-2 (PPCD2) is caused by heterozygous mutation in the COL8A2 gene (120252) on chromosome 1p34.
Posterior polymorphous corneal dystrophy-2 (PPCD2) is characterized by formation of blister-like lesions within the corneal endothelium or by regions of endothelial basement membrane thickening with associated corneal edema. The normal amitotic endothelial cells are replaced by epithelial-like cells that possess abundant intermediate filaments, desmosomes, and microvilli. The endothelium becomes multilayered and the abnormally proliferating cells may extend outwards from the cornea over the trabecular meshwork to cause glaucoma (summary by Biswas et al., 2001).
For a general phenotypic description and a discussion of genetic heterogeneity of PPCD, see PPCD1 (122000).
Biswas et al. (2001) reported a father and daughter with posterior polymorphous corneal dystrophy. Bilateral penetrating keratoplasty was performed in the proband in her twenties and in her father in his fifties.
The transmission pattern of PPCD2 in the family reported by Biswas et al. (2001) was consistent with autosomal dominant inheritance.
In 2 affected members of a family with posterior polymorphous corneal dystrophy, Biswas et al. (2001) identified a missense mutation in the triple helical domain of the COL8A2 gene (120252.0001), which encodes the alpha-2 chain of type VIII collagen, a short-chain collagen that is a component of endothelial basement membranes. They identified the same mutation in familial and sporadic cases of early-onset Fuchs endothelial corneal dystrophy (FECD; 136800). Biswas et al. (2001) suggested that the underlying pathogenesis of FECD and PPCD2 may be related to disturbance of the role of type VIII collagen in influencing the terminal differentiation of the neural crest-derived corneal endothelial cell.
In a family in which 1 member had PPCD2 and other members had early-onset FECD, Gottsch et al. (2005) found that all affected individuals were heterozygous for a leu450-to-trp (L450W) substitution (120252.0003).
Biswas, S., Munier, F. L., Yardley, J., Hart-Holden, N., Perveen, R., Cousin, P., Sutphin, J. E., Noble, B., Batterbury, M., Kielty, C., Hackett, A., Bonshek, R., Ridgway, A., McLeod, D., Sheffield, V. C., Stone, E. M., Schorderet, D. F., Black, G. C. M. Missense mutations in COL8A2, the gene encoding the alpha-2 chain of type VIII collagen, cause two forms of corneal endothelial dystrophy. Hum. Molec. Genet. 10: 2415-2423, 2001. [PubMed: 11689488] [Full Text: https://doi.org/10.1093/hmg/10.21.2415]
Gottsch, J. D., Sundin, O. H., Liu, S. H., Jun, A. S., Broman, K. W., Stark, W. J., Vito, E. C. L., Narang, A. K., Thompson, J. M., Magovern, M. Inheritance of a novel COL8A2 mutation defines a distinct early-onset subtype of Fuchs corneal dystrophy. Invest. Ophthal. Vis. Sci. 46: 1934-1939, 2005. [PubMed: 15914606] [Full Text: https://doi.org/10.1167/iovs.04-0937]