title: Mutations in KERA, encoding keratocan, cause cornea plana.
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.
authors.affiliation: Division of Human Cancer Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, Ohio, USA.
authors.forename: N S
authors.initials: NS
authors.lastname: Pellegata
authors.forename: J L
authors.initials: JL
authors.lastname: Dieguez-Lucena
authors.forename: T
authors.initials: T
authors.lastname: Joensuu
authors.forename: S
authors.initials: S
authors.lastname: Lau
authors.forename: K T
authors.initials: KT
authors.lastname: Montgomery
authors.forename: R
authors.initials: R
authors.lastname: Krahe
authors.forename: T
authors.initials: T
authors.lastname: Kivelä
authors.forename: R
authors.initials: R
authors.lastname: Kucherlapati
authors.forename: H
authors.initials: H
authors.lastname: Forsius
authors.forename: A
authors.initials: A
authors.lastname: de la Chapelle
mesh_terms: D000595:Amino Acid Sequence; D003094:Collagen / Q000378:metabolism; D003315:Cornea / Q000002:abnormalities* / Q000378:metabolism; D003316:Corneal Diseases / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism*; D018703:Founder Effect; D006801:Humans; D007930:Leucine / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D020161:Physical Chromosome Mapping; D011509:Proteoglycans / Q000235:genetics* / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D005136:Eye Proteins; C490948:KERA protein, human; D011509:Proteoglycans; D003094:Collagen; D007930:Leucine