Mutations in KERA, encoding keratocan, cause cornea plana

Specialized collagens and small leucine-rich proteoglycans (SLRPs) interact to produce the transparent corneal structure(1) In cornea plana, the forwa rd convex curvature is flattened, leading to a decrease in refraction(2). A more severe, recessively inherited form (CNA2; MIM 217300) and a milder, d ominantly inherited form (CNA1; MIM 121400) exist. CNA2 is a rare disorder with a worldwide distribution, but a high prevalence in the Finnish populat ion(3). The gene mutated in CNA2 was assigned by linkage analysis to 12q (r efs 4,5), where there is a cluster of several SLRP genes(6-9). We cloned tw o additional SLRP genes highly expressed in cornea: KERA (encoding keratoca n) 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 p remature stop codon that truncates the KERA protein. Our data establish tha t mutations in KERA cause CNA2. CNA1 patients had no mutations in these pro teoglycan genes.