title: 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.
abstract: 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.
authors.affiliation: Istituto di Genetica Molecolare, C.N.R., Alghero, Italy. cr@igm.ss.cnr.it
authors.forename: C
authors.initials: C
authors.lastname: Rozzo
authors.forename: M
authors.initials: M
authors.lastname: Fossarello
authors.forename: G
authors.initials: G
authors.lastname: Galleri
authors.forename: G
authors.initials: G
authors.lastname: Sole
authors.forename: A
authors.initials: A
authors.lastname: Serru
authors.forename: N
authors.initials: N
authors.lastname: Orzalesi
authors.forename: A
authors.initials: A
authors.lastname: Serra
authors.forename: M
authors.initials: M
authors.lastname: Pirastu
mesh_terms: D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics*; D016326:Extracellular Matrix Proteins; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics; D000099222:betaIG-H3 Protein
chemical_list: D016326:Extracellular Matrix Proteins; D009363:Neoplasm Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein