title: Granular corneal dystrophy with homozygous mutations in the kerato-epithelin gene.
abstract: OBJECTIVE
  To report a family with several members affected with granular corneal dystrophy Groenouw type 1. Three members of the family were affected with a severe placoid type of corneal dystrophy. To determine the relationship between gene mutations and phenotypic variations of the disease, we analyzed the kerato-epithelin gene.
  
  
  METHODS
  The pedigree included a consanguineous marriage of two affected individuals. The three family members affected with a severe form of corneal dystrophy were offspring of these parents. However, the phenotype of other affected family members was typical granular corneal dystrophy. We isolated genomic DNA from leukocytes of the family members. Exons of the keratoepithelin gene were amplified by the polymerase chain reaction and were analyzed using the single-strand conformation polymorphism technique. Mutations were identified by direct sequencing method and restriction digestion analysis.
  
  
  RESULTS
  The three severely affected family members exhibited homozygous mutations at codon 555 (arginine to tryptophan) in the keratoepithelin gene, whereas those with typical granular corneal dystrophy had the heterozygous mutation at the same codon. Unaffected family members did not have the mutation.
  
  
  CONCLUSIONS
  We determined that the severe phenotype of granular corneal dystrophy is caused by homozygous mutations in the kerato-epithelin gene. Clinical manifestation of the severe phenotype is a placoid type of corneal dystrophy and early recurrence after surgery. Granular corneal dystrophy appears to be the first ophthalmic disease in which homozygosity for a dominant allele has been genetically identified.
authors.affiliation: Department of Ophthalmology, Osaka University Medical School, Suita, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Okada
authors.forename: S
authors.initials: S
authors.lastname: Yamamoto
authors.forename: H
authors.initials: H
authors.lastname: Watanabe
authors.forename: Y
authors.initials: Y
authors.lastname: Inoue
authors.forename: M
authors.initials: M
authors.lastname: Tsujikawa
authors.forename: N
authors.initials: N
authors.lastname: Maeda
authors.forename: Y
authors.initials: Y
authors.lastname: Shimomura
authors.forename: K
authors.initials: K
authors.lastname: Nishida
authors.forename: S
authors.initials: S
authors.lastname: Kinoshita
authors.forename: Y
authors.initials: Y
authors.lastname: Tano
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003241:Consanguinity; D003315:Cornea / Q000473:pathology; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000473:pathology; D017931:DNA Primers / Q000737:chemistry; D016326:Extracellular Matrix Proteins; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017422:Sequence Analysis, DNA; D016212:Transforming Growth Factor beta / Q000235:genetics*; D000099222:betaIG-H3 Protein
chemical_list: D017931:DNA Primers; D016326:Extracellular Matrix Proteins; D009363:Neoplasm Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein