A common beta ig-h3 gene mutation (delta f540) in a large cohort of Sardinian Reis Bücklers corneal dystrophy patients. Mutations in brief no. 180. Online

Hum Mutat. 1998;12(3):215-6.


Reis-Bücklers' corneal dystrophy (RBCD) is a relatively rare autosomal dominant disease originating in the Bowman's membrane, which causes severe visual impairment. Recently RBCD, together with lattice corneal dystrophy type I (LCDI), granular corneal dystrophy (CDGG1) and Avellino stromal dystrophy (ASD), all mapped on 5q31, were found to be associated to four different mutations in the beta ig-h3 gene which codify for kerato-epithelin. We identified several cases of RBCD in Sardinia. We reconstructed through genealogical search two eight generation-families, originating from the same village (Arbus), indicating a common ancestor for RBCD in Sardinia. Linkage studies on these families confirmed the association of the disease with the 5q31 region. Sequence analysis of beta ig-h3 gene revealed a trinucleotide deletion in exon 12, corresponding to the loss of F540 in the protein sequence (delta F540). Our data describe a new mutation in the beta ig-h3 gene causing RBCD. This dominant negative mutation is located in the fourth internal repeat of kerato-epithelin which is a protein domain highly conserved across species. This suggests the basic role of this domain in maintaining the proper kerato-epithelin structure which when altered can cause the typical precipitates in the RBCD cornea.

MeSH terms

  • Chromosomes, Human, Pair 5 / genetics
  • Corneal Dystrophies, Hereditary / genetics*
  • Extracellular Matrix Proteins*
  • Humans
  • Mutation / genetics*
  • Neoplasm Proteins / genetics*
  • Transforming Growth Factor beta / genetics


  • Extracellular Matrix Proteins
  • Neoplasm Proteins
  • Transforming Growth Factor beta
  • betaIG-H3 protein