Alternative titles; symbols
SNOMEDCT: 419197009; ORPHA: 98964; DO: 8943;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 5q31.1 | Corneal dystrophy, lattice type I | 122200 | Autosomal dominant | 3 | TGFBI | 601692 |
A number sign (#) is used with this entry because of evidence that lattice corneal dystrophy type I (CDL1) is caused by heterozygous mutation in the gene encoding keratoepithelin (TGFBI; 601692) on chromosome 5q31.
Heterozygous mutation in the TGFBI gene causes several other forms of autosomal dominant corneal dystrophy.
Lattice corneal dystrophy type I (CDL1) is an autosomal dominant condition characterized by deposition of amyloid in the corneal stroma. Onset occurs in the first or second decade of life and progresses over time. The anterior stroma has rod-like or linear opacities. Recurrent erosions are common and central anterior stromal haze may develop with age. The lesions usually affect the anterior and central corneas, leaving a relatively normal periphery (summary by Lin et al., 2016).
Frayer and Blodi (1959) described a family with lattice corneal dystrophy. Grayish lines like cotton threads are mainly limited to a zone between the center of the cornea and the periphery, usually not extending to the limbus. Rounded dots with distinct borders are scattered everywhere. The cornea between opacities is relatively clear. Visual activity is usually normal in childhood. In this and the granular type (see 121900), the histologic findings are hyaline degeneration and absence of acid mucopolysaccharide deposition. The changes involve particularly the central portion of the cornea, becoming evident in adolescence and consisting of delicate, double-contoured, interdigitating, elongated deposits that form a reticular pattern in the corneal stroma. Recurrent corneal ulceration sometimes occurs. Progression to severe visual impairment by the fifth or sixth decade is the rule. No signs of systemic abnormality have been described.
Waring et al. (1978) and Gorevic et al. (1984) distinguished 3 inherited forms of lattice corneal dystrophy on clinical and histologic grounds: type I, the autosomal dominant form discussed here, which is not associated with systemic amyloidosis; type II, which is associated with systemic amyloidosis (the Finnish type; 105120); and type III (204870), the recessive form, which has an onset at age 70 to 90 years and is not associated with systemic amyloidosis.
Dinh et al. (1999) reviewed 50 excimer laser phototherapeutic keratectomy (PTK) procedures. Preoperative diagnoses included Reis-Bucklers dystrophy (see 121900), granular dystrophy (121900), anterior basement membrane dystrophy (121820), lattice dystrophy, and Schnyder crystalline dystrophy (121800). The authors concluded that PTK can restore and preserve useful visual function for a significant period of time in patients with anterior corneal dystrophies. Even though corneal dystrophies are likely to recur eventually after PTK, successful re-treatment with PTK is possible.
Stone et al. (1994) found that the gene for lattice corneal dystrophy type I maps to chromosome 5q, in the same region as the gene for granular corneal dystrophy Groenouw type I (CDGG1; 121900) and the atypical combined granular/lattice corneal dystrophy known as the Avellino form (CDA; 607541).
The transmission pattern of CDL1 in the families reported by Munier et al. (1997) was consistent with autosomal dominant inheritance.
In 2 families with autosomal dominant lattice corneal dystrophy type I, Munier et al. (1997) identified a mutation in the gene encoding keratoepithelin (R124C; 601692.0003). They postulated that the mutation resulted in amyloidogenic intermediates.
In an extensively studied African American family with lattice corneal dystrophy, Klintworth et al. (2004) and Aldave et al. (2004) reported 2 heterozygous mutations in the TGFBI gene (A546D; P551Q, 601692.0009).
Variant Studies
Kim et al. (2002) studied the molecular properties of wildtype and mutant TGFBI proteins: specifically, the arg124-to-leu (R124L; 601692.0007) (Reis-Bucklers corneal dystrophy (CDRB; 608470)), arg124-to-cys (R124C; 601692.0003) (CDL1), arg124-to-his (R124H; 601692.0004) (CDA), arg555-to-trp (R555W; 601692.0001) (CDGG1), and arg555-to-gln (R555Q; 601692.0002) (Thiel-Behnke corneal dystrophy (CDTB; 602082)) mutations commonly found in 5q31-linked corneal dystrophies. They found that the mutations did not significantly affect the fibrillar structure, interactions with other extracellular matrix proteins, or adhesion activity in cultured corneal epithelial cells. In addition, the mutations apparently produced degradation products similar to those of wildtype TGFBI. TGFBI polymerizes to form a fibrillar structure and strongly interacts with type I collagen (see 120150), laminin (see 150320), and fibronectin (135600). Mutations did not significantly affect these properties. Kim et al. (2002) concluded that mutant forms of TGFBI might require other cornea-specific factors to form the abnormal accumulations seen in 5q31-linked corneal dystrophies.
Exclusion Studies
In a large multigeneration Manitoba kindred of Belgian descent, Wiens et al. (1992) demonstrated that the gene causing autosomal dominant lattice corneal dystrophy without systemic amyloidosis was not linked to the gelsolin gene (GSN; 137350), which is mutated in the Finnish form of amyloidosis (105120).
Meretoja (1973) suggested the existence of 2 and perhaps 3 distinct forms of lattice corneal dystrophy without systemic abnormality. In type I, manifestation is early, i.e., in the first or second decade. In type II, manifestation is later with reasonably good visual acuity retained until age 50 to 70. The lattice lines in type II are thicker and fewer, leaving portions of the central cornea clear, with few or no spots or crystals. Patients have fewer erosions. Type III, of more questionable distinctness, is illustrated by the case of Wolter and Henderson (1963).
Aldave, A. J., Gutmark, J. G., Yellore, V. S., Affeldt, J. A., Meallet, M. A., Udar, N., Rao, N. A., Small, K. W., Klintworth, G. K. Lattice corneal dystrophy associated with the ala546asp and pro551gln missense changes in the TGFBI gene. Am. J. Ophthal. 138: 772-781, 2004. [PubMed: 15531312] [Full Text: https://doi.org/10.1016/j.ajo.2004.06.021]
Dinh, R., Rapuano, C. J., Cohen, E. J., Laibson, P. R. Recurrence of corneal dystrophy after excimer laser phototherapeutic keratectomy. Ophthalmology 106: 1490-1497, 1999. [PubMed: 10442892] [Full Text: https://doi.org/10.1016/S0161-6420(99)90441-4]
Frayer, W. C., Blodi, F. C. The lattice type of familial corneal degeneration: a histopathologic study. Arch. Ophthal. 61: 712-719, 1959. [PubMed: 13636566] [Full Text: https://doi.org/10.1001/archopht.1959.00940090714007]
Gorevic, P. D., Rodrigues, M. M., Krachmer, J. H., Green, C., Fujihara, S., Glenner, G. G. Lack of evidence for protein AA reactivity in amyloid deposits of lattice corneal dystrophy and amyloid corneal degeneration. Am. J. Ophthal. 98: 216-224, 1984. [PubMed: 6383050] [Full Text: https://doi.org/10.1016/0002-9394(87)90357-6]
Kim, J-E., Park, R-W., Choi, J-Y., Bae, Y-C., Kim, K-S., Joo, C-K., Kim, I-S. Molecular properties of wild-type and mutant beta-IG-H3 proteins. Invest. Ophthal. Vis. Sci. 43: 656-661, 2002. [PubMed: 11867580]
King, R. G., Jr., Geeraets, W. J. Lattice or Reis-Buecklers corneal dystrophy: a question of stromal pathology. Sth. Med. J. 62: 1163-1169, 1969. [PubMed: 4899144] [Full Text: https://doi.org/10.1097/00007611-196910000-00001]
Klintworth, G. K., Bao, W., Afshari, N. A. Two mutations in the TGFBI (BIGH3) gene associated with lattice corneal dystrophy in an extensively studied family. Invest. Ophthal. Vis. Sci. 45: 1382-1388, 2004. [PubMed: 15111592] [Full Text: https://doi.org/10.1167/iovs.03-1228]
Lin, Z.-N., Chen, J., Cui, H.-P. Characteristics of corneal dystrophies: a review from clinical, histological and genetic perspectives. Int. J. Ophthal. 9: 904-913, 2016. [PubMed: 27366696] [Full Text: https://doi.org/10.18240/ijo.2016.06.20]
Meretoja, J. Comparative histopathological and clinical findings in eyes with lattice corneal dystrophy of two different types. Ophthalmologica 165: 15-37, 1972. [PubMed: 4115977] [Full Text: https://doi.org/10.1159/000308469]
Meretoja, J. Inherited systemic amyloidosis with lattice corneal dystrophy. Acad. Dissertation: Helsinki (pub.) 1973.
Munier, F. L., Korvatska, E., Djemai, A., Le Paslier, D., Zografos, L., Pescia, G., Schorderet, D. F. Kerato-epithelin mutations in four 5q31-linked corneal dystrophies. Nature Genet. 15: 247-251, 1997. [PubMed: 9054935] [Full Text: https://doi.org/10.1038/ng0397-247]
Ramsay, R. M. Familial corneal dystrophy, lattice type. Trans. Canad. Ophthal. Soc. 23: 222-229, 1960. [PubMed: 13739412]
Stone, E. M., Mathers, W. D., Rosenwasser, G. O. D., Holland, E. J., Folberg, R., Krachmer, J. H., Nichols, B. E., Gorevic, P. D., Taylor, C. M., Streb, L. M., Fishbaugh, J. A., Daley, T. E., Sucheski, B. M., Sheffield, V. C. Three autosomal dominant corneal dystrophies map to chromosome 5q. Nature Genet. 6: 47-51, 1994. [PubMed: 8136834] [Full Text: https://doi.org/10.1038/ng0194-47]
Waring, G. O., III, Rodrigues, M. M., Laibson, P. R. Corneal dystrophies. I. Dystrophies of the epithelium, Bowman's layer and stroma. Surv. Ophthal. 23: 71-122, 1978. [PubMed: 360456] [Full Text: https://doi.org/10.1016/0039-6257(78)90090-5]
Wiens, A., Marles, S., Safneck, J., Kwiatkowski, D. J., Maury, C. P. J., Zelinski, T., Philipps, S., Ekins, M. B., Greenberg, C. R. Exclusion of the gelsolin gene on 9q32-34 as the cause of familial lattice corneal dystrophy type I. Am. J. Hum. Genet. 51: 156-160, 1992. [PubMed: 1319113]
Wolter, J. R., Henderson, J. W. Lattice dystrophy of the cornea: a primary hyaline degeneration of corneal nerves and superficial stroma cells. Am. J. Ophthal. 55: 475-484, 1963. [PubMed: 14001686]