title: Mutational screening of VSX1, SPARC, SOD1, LOX, and TIMP3 in keratoconus.
abstract: OBJECTIVE
  To evaluate the involvement of Visual System Homeobox 1 (VSX1), Secreted Protein Acidic and Rich in Cysteine (SPARC), Superoxide Dismutase 1 (SOD1), Lysyl Oxidase (LOX), and Tissue Inhibitor of Metalloproteinase 3 (TIMP3) in sporadic and familial keratoconus.
  
  
  METHODS
  Mutational analysis of the five genes was performed by sequencing and fragment analysis in a large cohort of 302 Italian patients, with a diagnosis of keratoconus based on clinical examination and corneal topography. The variants identified in VSX1 and SPARC were also assessed in the available relatives of the probands.
  
  
  RESULTS
  A novel mutation p.G239R and previously reported mutations were found in VSX1. Novel and already reported variants were identified in SPARC and SOD1, whose pathogenic significance has not been established. No pathogenic variants have been identified in LOX and TIMP3.
  
  
  CONCLUSIONS
  Molecular analysis of the five genes in a cohort of 225 sporadic and 77 familial keratoconus cases confirms the possible pathogenic role of VSX1 though in a small number of patients; a possible involvement of LOX and TIMP3 could be excluded; and the role played by SOD1 and SPARC in determining the disease as not been definitively clarified. Further studies are required to identify other important genetic factors involved in the pathogenesis and progression of the disease that in the authors' opinion, and according with several authors, should be considered as a complex disease.
authors: Unità di Genetica Medica, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors: Patrizia
authors: P
authors: De Bonis
authors: Antonio
authors: A
authors: Laborante
authors: Costantina
authors: C
authors: Pizzicoli
authors: Raffaella
authors: R
authors: Stallone
authors: Raffaela
authors: R
authors: Barbano
authors: Costanza
authors: C
authors: Longo
authors: Emilio
authors: E
authors: Mazzilli
authors: Leopoldo
authors: L
authors: Zelante
authors: Luigi
authors: L
authors: Bisceglia
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D015331:Cohort Studies; D003315:Cornea / Q000378:metabolism* / Q000473:pathology; D019781:Corneal Topography; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005820:Genetic Testing; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007558:Italy; D007640:Keratoconus / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D015676:Osteonectin / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics*; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics*
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D015676:Osteonectin; C000606290:SOD1 protein, human; C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3; C491583:VSX1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D008249:Protein-Lysine 6-Oxidase