title: On the role of kerato-epithelin in the pathogenesis of 5q31-linked corneal dystrophies.
abstract: OBJECTIVE
  Recently, the authors identified a gene, BIGH3, in which different mutations cause a group of hereditary corneal dystrophies: lattice type I and IIIA (CDLI and CDLIIIA), granular Groenouw type I (CDGGI), Avellino (CDA), and Reis-Bücklers' (CDRB). All these disorders are characterized by the progressive accumulation of corneal deposits with different structural organization. Experiments were conducted to determine the role of kerato-epithelin (KE), the product of BIGH3, in the pathogenesis of the diseases.
  
  
  METHODS
  KE-15 and KE-2, two rabbit antisera raised against peptides from the 69-364 and 426 - 682 amino acid regions of KE respectively, were used for immunohistology of the corneas obtained after keratoplasty in six CDLI patients, three CDGGI patients, and one CDA patient.
  
  
  RESULTS
  The nonamyloid deposits observed in CDGGI stained intensively with KE-15 and KE-2, whereas the amyloid deposits in all analyzed CDLI corneas reacted to KE-2 but not to KE-15. In the CDA cornea, where amyloid and nonamyloid inclusions were present, positive staining with both antisera was observed.
  
  
  CONCLUSIONS
  Pathologic amyloid and nonamyloid deposits observed in CDLI, CDGGI-, and CDA-affected corneas are caused by KE accumulation. Different staining patterns of amyloid and nonamyloid deposits observed with antibodies against the amino and carboxyl termini of KE suggest that two mechanisms of KE misfolding are implicated in the pathogenesis of 5q31-linked corneal dystrophies.
authors.affiliation: Unit of Molecular Genetics, University of Lausanne, Switzerland.
authors.forename: E
authors.initials: E
authors.lastname: Korvatska
authors.forename: F L
authors.initials: FL
authors.lastname: Munier
authors.forename: P
authors.initials: P
authors.lastname: Chaubert
authors.forename: M X
authors.initials: MX
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Mashima
authors.forename: M
authors.initials: M
authors.lastname: Yamada
authors.forename: S
authors.initials: S
authors.lastname: Uffer
authors.forename: L
authors.initials: L
authors.lastname: Zografos
authors.forename: D F
authors.initials: DF
authors.lastname: Schorderet
mesh_terms: D000682:Amyloid / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002895:Chromosomes, Human, Pair 5; D003315:Cornea / Q000378:metabolism; D003317:Corneal Dystrophies, Hereditary / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D017931:DNA Primers / Q000737:chemistry; D016326:Extracellular Matrix Proteins; D005347:Fibroblasts / Q000378:metabolism; D008040:Genetic Linkage; D006801:Humans; D007124:Immunoenzyme Techniques; D015948:Keratoplasty, Penetrating; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000502:physiology*; D010446:Peptide Fragments; D011817:Rabbits; D016212:Transforming Growth Factor beta / Q000502:physiology*; D000099222:betaIG-H3 Protein
chemical_list: D000682:Amyloid; D017931:DNA Primers; D016326:Extracellular Matrix Proteins; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein