The morphogenesis of granular and lattice corneal dystrophy - A mutation combination hypothesis

Mutations in the BIGH3 gene encoding for keratoepithelin protein have been described in different corneal dystrophies viz. granular corneal dystrophy, lattice corneal dystrophy, and their different clinical subtypes. Even though linked to the BIGH3 gene, the role of BIGH3 gene in the pathogenesis of corneal lattice dystrophy and corneal granular dystrophy remains to be elucidated. We describe the probable functions of a mutated BIGH3 gene in disease pathogenesis, postulate the existence of other phenotype modifier mutations in these dystrophies, and how the coinheritance of these mutations in different combinations along with a normal/mutated BIGH3 gene can lead to the different morphologic patterns seen in these corneal dystrophies and their subtypes.