A novel mutation at codon 124 (R124L) in the BIGH3 gene is associated with a superficial variant of granular corneal dystrophy.

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Abstract
FOUR DISORDERS of the corneal stroma that are linked to an autosomal dominant inheritance result from mutations in the human transforming growth factor β–induced gene (BIGH3), of which the product is keratoepithelin. These disorders are granular corneal dystrophy (GCD), associated with R555W; lattice corneal dystrophy type 1, associated with R124C; Avellino corneal dystrophy, associated with R124H; and Reis-Bücklers corneal dystrophy (RBCD), associated with R555Q mutation.1 Each of these 4 mutations affects the CpG dinucleotide of an arginine codon. Two types of the R124 mutation in the BIGH3 gene are associated with 2 different clinical phenotypes of corneal dystrophies, Avellino corneal dystrophy or lattice corneal dystrophy type 1,2,3 both of which are associated with amyloid deposition. Thus, keratoepithelin associated with the R124 mutation may form amyloidogenic intermediates that precipitate in the cornea.