title: Kerato-epithelin mutations in four 5q31-linked corneal dystrophies.
abstract: Granular dystrophy Groenouw type I (CDGG1), Reis-Bücklers (CDRB), lattice type I (CDL1) and Avellino (ACD) are four 5q31-linked human autosomal dominant corneal dystrophies. Clinically, they show progressive opacification of the cornea leading to severe visual handicap. The nature of the deposits remains unknown in spite of amyloid aetiology ascribed to the last two. We generated a YAC contig of the linked region and, following cDNA selection, recovered the beta ig-h3 gene. In six affected families we identified missense mutations. All detected mutations occurred at the CpG dinucleotide of two arginine codons: R555W in one CDGG1, R555Q in one CDRB, R124C in two CDL1 and R124H in two ACD families. This suggests, as the last two diseases are characterized by amyloid deposits, that R124 mutated kerato-epithelin (the product of beta ig-h3) forms amyloidogenic intermediates that precipitate in the cornea. Our data establish a common molecular origin for the 5q31-linked corneal dystrophies.
authors.affiliation: Unit of Molecular Genetics, CHUV, Lausanne, Switzerland.
authors.forename: F L
authors.initials: FL
authors.lastname: Munier
authors.forename: E
authors.initials: E
authors.lastname: Korvatska
authors.forename: A
authors.initials: A
authors.lastname: Djemaï
authors.forename: D
authors.initials: D
authors.lastname: Le Paslier
authors.forename: L
authors.initials: L
authors.lastname: Zografos
authors.forename: G
authors.initials: G
authors.lastname: Pescia
authors.forename: D F
authors.initials: DF
authors.lastname: Schorderet
mesh_terms: D017398:Alternative Splicing; D001483:Base Sequence; D002478:Cells, Cultured; D002874:Chromosome Mapping; D018244:Chromosomes, Artificial, Yeast; D002895:Chromosomes, Human, Pair 5; D003315:Cornea / Q000378:metabolism; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics*; D017931:DNA Primers; D015226:Dinucleoside Phosphates; D005091:Exons; D016326:Extracellular Matrix Proteins; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein
chemical_list: D017931:DNA Primers; D015226:Dinucleoside Phosphates; D016326:Extracellular Matrix Proteins; D009363:Neoplasm Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein; C015772:CpG dinucleotide