BIGH3 gene analysis in the differential diagnosis of corneal dystrophies

Purpose. To identify the mutation in the keratoepithelin gene for proper diagnosis of granular corneal dystrophies. Methods. Four generations of a single family with corneal dystrophy were analyzed. Fourteen family members were examined and 11 were found to be affected by clinical evaluation. Genetic DNA was extracted from proband's leukocytes for molecular analysis. Exons 4 and 12 of the BIGH(3) gene were amplified then directly sequenced. Results. The clinical appearance of corneas consisted of grayish white granules with sharp borders, fine dots, and radial lines in the superficial part of the central corneal stroma, which resembles granular and Avellino corneal dystrophies. Performing BIGH(3) gene analysis, we observed a C-to-T transition at position 1710 (CGG to TGG) producing R555W mutation, which is a hot spot for granular corneal dystrophy. Conclusion. Direct clinical examination may be insignificant in the proper diagnosis of corneal dystrophies, and molecular genetic approach may be required.