ORPHA: 53691; DO: 0060287;
Cytogenetic location: 12q21.33 Genomic coordinates (GRCh38): 12:88,600,001-92,200,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 12q21.33 | Cornea plana 1, autosomal dominant | 121400 | Autosomal dominant | 2 |
Cornea plana is clinically characterized by reduced corneal curvature leading in most cases to hyperopia, hazy corneal limbus, and arcus lipoides at an early age. CNA1, an autosomal dominant form of the disorder, is mild (summary by Tahvanainen et al., 1996).
Genetic Heterogeneity of Cornea Plana
Also see CNA2 (217300), an autosomal recessive form of the disorder, which is severe and frequently associated with additional ocular manifestations.
Larsen and Eriksen (1949) described 13 patients in 3 generations of each of 2 families. Eriksson et al. (1973) described families.
Waizenegger et al. (1995) described autosomal dominant cornea plana with conjunctival xerosis in an Albanian family.
Tahvanainen et al. (1996) described a Cuban pedigree in which 14 members were affected with dominantly inherited cornea plana.
Tahvanainen et al. (1996) compared dominant and recessive forms of cornea plana in the Finnish population by measuring horizontal corneal refraction values in diopters (D). A control population of 473 individuals had a mean value of 43.4 (SD = 1.5 D) for men and 43.7 (SD = 1.6 D) for women, whereas in 51 subjects affected with CNA2, the mean value was 29.9 (SD = 5.1 D), and in 5 subjects affected with CNA1, the mean value was 37.8 (SD = 1.6 D).
Aldave et al. (2007) reported a Hispanic family segregating autosomal dominant cornea plana. All 5 affected members demonstrated an average corneal dioptric power less that 39 D, as well as one or more of the following anomalies: high hyperopia (average spherical equivalent refractive error +6.33 D), strabismus, microcornea, posterior corneal stromal haze, posterior embryotoxon, iridocorneal adhesions, iris nodules, iris atrophy, and pupillary irregularities.
The transmission pattern of CNA1 in the Cuban family reported by Tahvanainen et al. (1996) and the Hispanic family reported by Aldave et al. (2007) was consistent with autosomal recessive inheritance.
By linkage analysis in 2 Finnish families with autosomal dominant cornea plana, Tahvanainen et al. (1996) excluded the CNA2 region on chromosome 12.
By linkage analysis in a Cuban pedigree with autosomal dominant cornea plana, Tahvanainen et al. (1996) found linkage to the immediate vicinity of markers D12S82 and D12S351 on 12q, which is the same region of 3 cM or less to which CNA2 had been assigned in Finnish families.
Exclusion Studies
Pellegata et al. (2000) found no mutations in the KERA gene (603288), which is mutant in CNA2, in Cuban patients with CNA1.
In a multigenerational Hispanic family segregating autosomal dominant cornea plana, Aldave et al. (2007) identified no causative mutations in 6 candidate genes, including KERA.
Aldave, A. J., Sonmez, B., Bourla, N., Schultz, G., Papp, J. C., Salem, A. K., Rayner, S. A., Yellore, V. S. Autosomal dominant cornea plana is not associated with pathogenic mutations in DCN, DSPG3, FOXC1, KERA, LUM, or PITX2. Ophthalmic Genet. 28: 57-67, 2007. [PubMed: 17558846] [Full Text: https://doi.org/10.1080/13816810701351321]
Eriksson, A. W., Lehmann, W., Forsius, H. Congenital cornea plana in Finland. Clin. Genet. 4: 301-310, 1973. [PubMed: 4747808] [Full Text: https://doi.org/10.1111/j.1399-0004.1973.tb01924.x]
Larsen, V., Eriksen, A. W. Cornea plana. Acta Ophthal. 27: 275-286, 1949. [PubMed: 18142199] [Full Text: https://doi.org/10.1111/j.1755-3768.1949.tb05835.x]
Pellegata, N. S., Dieguez-Lucena, J. L., Joensuu, T., Lau, S., Montgomery, K. T., Krahe, R., Kivela, T., Kucherlapati, R., Forsius, H., de la Chapelle, A. Mutations in KERA, encoding keratocan, cause cornea plana. Nature Genet. 25: 91-95, 2000. [PubMed: 10802664] [Full Text: https://doi.org/10.1038/75664]
Tahvanainen, E., Forsius, H., Kolehmainen, J., Damsten, M., Fellman, J., de la Chapelle, A. The genetics of cornea plana congenita. J. Med. Genet. 33: 116-119, 1996. [PubMed: 8929947] [Full Text: https://doi.org/10.1136/jmg.33.2.116]
Tahvanainen, E., Villanueva, A. S., Forsius, H., Salo, P., de la Chapelle, A. Dominantly and recessively inherited cornea plana congenita map to the same small region of chromosome 12. Genome Res. 6: 249-254, 1996. [PubMed: 8723718] [Full Text: https://doi.org/10.1101/gr.6.4.249]
Waizenegger, U. R., Kohnen, T., Weidle, E. G., Schutte, E. Kongenitale familiare Cornea plana mit Ptosis, peripherer Sklerokornea und Bindehaut-Xerose. Klin. Monatsbl. Augenheilkd. 207: 111-116, 1995. [PubMed: 7474773] [Full Text: https://doi.org/10.1055/s-2008-1035357]