title: Clinical and molecular characterization of a family with autosomal recessive cornea plana.
abstract: BACKGROUND
  Autosomal recessive cornea plana is characterized by a flattened corneal surface associated with hyperopia and various anterior segment abnormalities. Mutations have been detected in the keratocan gene (KERA), a member of the small leucine-rich proteoglycan family.
  
  
  OBJECTIVE
  To clinically and molecularly characterize a consanguineous family of Hispanic origin in which 3 individuals are affected with cornea plana.
  
  
  METHODS
  Clinical ophthalmic examination, including corneal topography and axial eye length measurement, was performed on 7 family members. Molecular analysis of KERA was performed on DNA from each family member who had been examined.
  
  
  RESULTS
  All 3 affected individuals showed extreme flattening of the cornea (< 36 diopters [D]), normal axial eye lengths, and hyperopia greater than 6.25 D (spherical equivalent). Anterior segment abnormalities included scleralization of the cornea and central iris strands to the corneal endothelium. Affected individuals were homozygous for a novel mutation in KERA. The sequence change was found in exon 2, which results in an asparagine to aspartic acid change at codon 131. This amino acid change occurs within a highly conserved leucine-rich repeat of keratocan.
  
  
  CONCLUSIONS
  The cause of disease in this family is likely to be a mutation in exon 2 of KERA. Other mutations in KERA known to cause cornea plana also fall within the region encoding the leucine-rich repeat motifs and are predicted to affect the tertiary structure of the protein.
  
  
  CONCLUSIONS
  This is the first report of the identification of a mutation within KERA in a family of Hispanic origin with autosomal recessive cornea plana. Although the vast majority of cases of cornea plana are in individuals of Finnish descent, this report demonstrates the occurrence of the disease in other populations.
authors.affiliation: Division of Molecular Genetics, Institute of Ophthalmology, University College London, London, England, UK.
authors.forename: Neil D
authors.initials: ND
authors.lastname: Ebenezer
authors.forename: Chetankumar B
authors.initials: CB
authors.lastname: Patel
authors.forename: Seenu M
authors.initials: SM
authors.lastname: Hariprasad
authors.forename: Li L
authors.initials: LL
authors.lastname: Chen
authors.forename: Reshma J
authors.initials: RJ
authors.lastname: Patel
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Hardcastle
authors.forename: Richard C
authors.initials: RC
authors.lastname: Allen
mesh_terms: D000595:Amino Acid Sequence; D002648:Child; D003241:Consanguinity; D003315:Cornea / Q000002:abnormalities / Q000473:pathology; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics*; D019781:Corneal Topography; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005124:Eye Abnormalities / Q000175:diagnosis / Q000235:genetics; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011509:Proteoglycans / Q000235:genetics*
chemical_list: C490948:KERA protein, human; D011509:Proteoglycans