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

To identify the mutation in a human transforming growth factor beta-induced gene (BIGH3) in a Japanese family with a severe form of granular corneal dystrophy of early onset associated with recurrent corneal erosions.

The tentative clinical diagnosis in this family was Reis-Bücklers corneal dystrophy; 4 persons affected with this disorder have been identified in 4 generations, and 3 of the 4 were examined. The proband underwent keratoplasties in our hospital (Keio University Hospital, Tokyo, Japan).

The BIGH3 gene was examined for a mutation by the polymerase chain reaction and direct sequencing. Corneal buttons of the proband were stained and examined by electron microscopy.

Three affected persons were shown to have a heterozygous G-->T transversion at the second nucleotide position of codon 124 (Arg-->Leu) of the BIGH3 gene. In the proband, corneal deposits between the epithelium and the Bowman layer stained red with Masson trichrome stain. Electron microscopy revealed numerous electron-dense, rod-shaped bodies next to the epithelial basement membrane but no curly fibers suggestive of Thiel-Behnke dystrophy.

A novel R124L mutation of the BIGH3 gene was associated in this family with a superficial variant of granular corneal dystrophy.

This mutation causes a severe form of superficial granular corneal dystrophy by producing abnormal keratoepithelin between the epithelium and the Bowman layer and thus clinical similarities to Reis-Bücklers corneal dystrophy.