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Mutations in KERA, encoding keratocan, cause cornea plana

Nature Geneticsvolume 25pages9195 (2000) | Download Citation



Specialized collagens and small leucine-rich proteoglycans (SLRPs) interact to produce the transparent corneal structure1. In cornea plana, the forward convex curvature is flattened, leading to a decrease in refraction2. 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 population3. The gene mutated in CNA2 was assigned by linkage analysis to 12q (refs 4,5), where there is a cluster of several SLRP genes6,7,8,9. 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.

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We thank the patients and their families for cooperation; R. Chadwick, C. Johnson and B. Yuan for sequencing and data assembly assistance; Y. Huang and J. Lockman for technical assistance; I. Maumenee, J. Hecht, A. Sigler-Villanueva and E.-M. Sankila for providing materials; and P. Kaumaya, K. Mrozek, S. Tanner and P. Peltomäki for helpful discussions. N.S.P. was supported in part by a fellowship from the ACSBI-UICC. This work was supported by grants from the National Institutes of Health (NG1763 and P30 CA16058) and the Academy of Finland.

Author information


  1. Division of Human Cancer Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, Ohio, USA

    • Natalia S. Pellegata
    • , Ralf Krahe
    •  & Albert de la Chapelle
  2. Folkhälsan Institute of Genetics, Helsinki, Finland

    • Jose L. Dieguez-Lucena
    • , Tarja Joensuu
    • , Henrik Forsius
    •  & Albert de la Chapelle
  3. Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, New York, USA

    • Stephanie Lau
    • , Kate T. Montgomery
    •  & Raju Kucherlapati
  4. Department of Ophthalmology, University Hospital of Helsinki, Helsinki, Finland

    • Tero Kivelä


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Correspondence to Albert de la Chapelle.

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