title: Corneal amyloidosis caused by Leu518Pro mutation of betaig-h3 gene.
abstract: OBJECTIVE
  To report a Japanese family diagnosed clinically as having lattice corneal dystrophy type I (LCDI) in which a Leu518Pro mutation in the betaig-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 betaig-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 betaig-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.
  
  
  CONCLUSIONS
  The Leu518Pro mutated betaig-h3 forms amyloidogeneic intermediates which precipitate in the cornea and gives rise to a clinical appearance of LCDI.
authors.affiliation: Department of Ophthalmology, Nagoya University School of Medicine, Aichi, Japan. kojihira@med.nagoya-u.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Hirano
authors.forename: Y
authors.initials: Y
authors.lastname: Hotta
authors.forename: K
authors.initials: K
authors.lastname: Fujiki
authors.forename: A
authors.initials: A
authors.lastname: Kanai
mesh_terms: D000293:Adolescent; D000328:Adult; D000686:Amyloidosis / Q000235:genetics* / Q000473:pathology; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000473:pathology; D016326:Extracellular Matrix Proteins; D005260:Female; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein
chemical_list: D016326:Extracellular Matrix Proteins; D009363:Neoplasm Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein