title: Mutations in the UBIAD1 gene on chromosome short arm 1, region 36, cause Schnyder crystalline corneal dystrophy.
abstract: OBJECTIVE
  Schnyder crystalline corneal dystrophy (SCCD; MIM 121800) is a rare autosomal dominant disease characterized by an abnormal increase in cholesterol and phospholipid deposition in the cornea, leading to progressive corneal opacification. Although SCCD has been mapped to a genetic interval between markers D1S1160 and D1S1635, reclassification of a previously unaffected individual expanded the interval to D1S2667 and included nine additional genes. Three candidate genes that may be involved in lipid metabolism and/or are expressed in the cornea were analyzed.
  
  
  METHODS
  DNA samples were obtained from six families with clinically confirmed SCCD. Analysis of FRAP1, ANGPTL7, and UBIAD1 was performed by PCR-based DNA sequencing, to examine protein-coding regions, RNA splice junctions, and 5' untranslated region (UTR) exons.
  
  
  RESULTS
  No disease-causing mutations were found in the FRAP1 or ANGPTL7 gene. A mutation in UBIAD1 was identified in all six families: Five families had the same N102S mutation, and one family had a G177R mutation. Predictions of the protein structure indicated that a prenyl-transferase domain and several transmembrane helices are affected by these mutations. Each mutation cosegregated with the disease in four families with DNA samples from both affected and unaffected individuals. Mutations were not observed in 100 control DNA samples (200 chromosomes).
  
  
  CONCLUSIONS
  Nonsynonymous mutations in the UBIAD1 gene were detected in six SCCD families, and a potential mutation hot spot was observed at amino acid N102. The mutations are expected to interfere with the function of the UBIAD1 protein, since they are located in highly conserved and structurally important domains.
authors.affiliation: Kresge Eye Institute, The Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI 48201, USA. jweiss@med.wayne.edu
authors.forename: Jayne S
authors.initials: JS
authors.lastname: Weiss
authors.forename: Howard S
authors.initials: HS
authors.lastname: Kruth
authors.forename: Helena
authors.initials: H
authors.lastname: Kuivaniemi
authors.forename: Gerard
authors.initials: G
authors.lastname: Tromp
authors.forename: Peter S
authors.initials: PS
authors.lastname: White
authors.forename: R Scott
authors.initials: RS
authors.lastname: Winters
authors.forename: Walter
authors.initials: W
authors.lastname: Lisch
authors.forename: Wolfram
authors.initials: W
authors.lastname: Henn
authors.forename: Elke
authors.initials: E
authors.lastname: Denninger
authors.forename: Matthias
authors.initials: M
authors.lastname: Krause
authors.forename: Paul
authors.initials: P
authors.lastname: Wasson
authors.forename: Neil
authors.initials: N
authors.lastname: Ebenezer
authors.forename: Sunil
authors.initials: S
authors.lastname: Mahurkar
authors.forename: Michael L
authors.initials: ML
authors.lastname: Nickerson
mesh_terms: D000091308:Angiopoietin-Like Protein 6; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D001112:Arcus Senilis / Q000235:genetics*; D001685:Biological Factors / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics*; D004252:DNA Mutational Analysis; D004122:Dimethylallyltranstransferase; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D058570:TOR Serine-Threonine Kinases
chemical_list: C477601:ANGPTL6 protein, human; D000091308:Angiopoietin-Like Protein 6; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D001685:Biological Factors; D002352:Carrier Proteins; D011506:Proteins; D004122:Dimethylallyltranstransferase; C425464:UBIAD1 protein, human; D017853:Phosphotransferases (Alcohol Group Acceptor); C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases