Purpose: The aim of this study was to analyze the relevant gene mutations in a Chinese family with special phenotypic variants of granular corneal dystrophy type 2 with cornea guttata. Methods: A total of 11 individuals from the affected family underwent complete ophthalmic examination. Genomic DNA was extracted from peripheral leukocytes of affected and unaffected family members. High-throughput sequencing was performed to screen for mutations in 290 genes associated with inherited ophthalmic diseases. Results were validated by bidirectional Sanger sequencing. Results: An Arg124His (R124H) mutation of the transforming growth factor beta-induced gene was identified in three members of the affected family: the proband (II-1), his mother (I-2), and his son (III-1). The eyes of the proband and his mother had bilateral superficial whitish ring patches with clear centers occupying their central corneas and appeared to be discoid or ring shaped. In addition, specular microscopic examination showed the presence of dark, round bodies. In vivo confocal microscopy showed some hyporeflective round images (cornea guttata), containing occasionally central highlight, in the proband, his mother, and one of his elder sisters. Conclusion: We report, for the first time, atypical granular corneal dystrophy type 2 with cornea guttata associated with a single R124H mutation in a Chinese family. Our findings emphasize that genotyping is essential for the accurate diagnosis and classification of granular corneal dystrophy type 2.
Impaired autophagy and delayed autophagic clearance of transforming growth factor β-induced protein (TGFBI) in granular corneal dystrophy type 2
