Corneal amyloidosis caused by Leu518Pro mutation of βig-h3 gene

Aim - To report a Japanese family diagnosed clinically as having lattice corneal dystrophy type I (LCDI) in which a Leu518Pro mutation in the βig-h3 gene and not the R124C mutation reported previously was found. Methods - Molecular genetic analysis was performed on DNA extracted from peripheral leucocytes from four members (three affected and one unaffected) of a family. Exon 4 of the βig-h3 gene was amplified by PCR and directly sequenced. Histopathological study was performed on the corneal tissue from the proband obtained during deep lamellar keratoplasty. Results - All the affected members were clinically diagnosed as having LCDI, and the pedigree indicated an autosomal dominant inheritance. A heterozygous single base pair transition (CTG to CCG, leucine to proline) was detected in codon 518 of the βig-h3 gene in the three affected members, and not in the unaffected member. No mutation was found in codon 124. Amyloid deposits were observed between the collagen bundles of the corneal stroma and were seen to extend deep into the stroma. Conclusion - The Leu518Pro mutated βig-h3 forms amyloidogeneic intermediates which precipitate in the cornea and gives rise to a clinical appearance of LCDI.