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Objective: To detect potential mutation in a large Chinese pedigree affected with congenital corneal dystrophy., Methods: Two patients from the pedigree were subjected to whole exome sequencing to determine the candidate gene. Suspected mutation was verified in 13 additional members by directional Sanger sequencing. Ccorrelation between genotype and phenotype was explored., Results: A missense mutation, c.1877A>C (p.His626Pro), was detected in exon 14 of the TGFBI gene in 8 patients from the pedigree, but not in five unaffected members and 100 unrelated healthy controls. Respectively, the mutation was predicted as "affecting protein function", "probably damaging" and "disease causing" by SIFT, PolyPhen-2 and MutationTaster., Conclusion: The c.1877A>C mutation of the TGFBI gene probably underlies the disease in this pedigree.

Keratoplasty specimens form 12 patients with macular corneal dystrophy, 1 patient with systemic glycosaminoglycan stored disease and 12 cases of normal cornea were studied by electron-histochemistry. The results showed that the normal cornea contains chondroitin sulfate in the basement membrane and bowman's membrane, Keratan sulfate and chondroitin sulfate between the collagen fibrils of strome, heparan sulfate on the cell membranes of various cells, and hyaluronic acid on the surface of endothelial cell. The chondroitin sulfate of the stroma of macular corneal dystrophy increases, but the keratan sulfate is absent. The keratocytes and endothelial cells of macular corneal dystrophy synthesize fibrillogranular material and abnormal glycosaminoglycan. The heparan sulfate is stored in the cytoplasm of corneal epithelial cell and keratocyte of systemic glycosaminoglycan stored disease and absent on the membrane of involved cells. The authors suggest that glycosaminoglycan play important role in maintaining corneal transparency and the changes of distribution, character and quantity of glycosaminoglycan in the cornea cause corneal opaqueness.

Keratoplasty specimens from 19 patients with macular corneal dystrophy (MCD), 11 patients with lattice corneal dystrophy (LCD) and 2 patients with granular corneal dystrophy (GCD) were examined by combinations of histochemistry, electron microscopy and electron--histochemistry. Electron histochemistry disclosed that the deposits of MCD have sulfate chondroitin and another hyaluronidase--resistant glycoaminoglycan and that the deposits of LCD have a little sulfate chondroitin. The authors suggest: (1) the possible pathologic mechanism of MCD is that the keratocytes and endothelial cells synthesize abnormal fibrillogranular material which consists of glycoaminoglycan, glycoprotein and lipid; (2) LCD is a primary localized corneal amyloidosis in which the amyloid deposits may result from corneal epithelial cells and keratocytes with a little sulfate chondroitin; (3) the deposits synthesized by corneal epithelial cells and keratocytes in GCD may result from a genetic defect in processing or synthesizing proteins.