Mutations in KERA, encoding keratocan, cause cornea plana

Nat Genet. 2000 May;25(1):91-5. doi: 10.1038/75664.

Abstract

Specialized collagens and small leucine-rich proteoglycans (SLRPs) interact to produce the transparent corneal structure. In cornea plana, the forward convex curvature is flattened, leading to a decrease in refraction. A more severe, recessively inherited form (CNA2; MIM 217300) and a milder, dominantly inherited form (CNA1; MIM 121400) exist. CNA2 is a rare disorder with a worldwide distribution, but a high prevalence in the Finnish population. The gene mutated in CNA2 was assigned by linkage analysis to 12q (refs 4, 5), where there is a cluster of several SLRP genes. We cloned two additional SLRP genes highly expressed in cornea: KERA (encoding keratocan) in 12q and OGN (encoding osteoglycin) in 9q. Here we report mutations in KERA in 47 CNA2 patients: 46 Finnish patients are homozygous for a founder missense mutation, leading to the substitution of a highly conserved amino acid; and one American patient is homozygous for a mutation leading to a premature stop codon that truncates the KERA protein. Our data establish that mutations in KERA cause CNA2. CNA1 patients had no mutations in these proteoglycan genes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Collagen / metabolism
  • Cornea / abnormalities*
  • Cornea / metabolism
  • Corneal Diseases / genetics*
  • Eye Proteins / genetics*
  • Eye Proteins / metabolism*
  • Founder Effect
  • Humans
  • Leucine / metabolism
  • Molecular Sequence Data
  • Mutation / genetics*
  • Physical Chromosome Mapping
  • Proteoglycans / genetics*
  • Proteoglycans / metabolism*
  • Sequence Alignment

Substances

  • Eye Proteins
  • KERA protein, human
  • Proteoglycans
  • Collagen
  • Leucine

Associated data

  • GENBANK/AF202166
  • GENBANK/AF202167
  • GENBANK/AF205403