title: Three VSX1 gene mutations, L159M, R166W, and H244R, are not associated with keratoconus.
abstract: OBJECTIVE
  Three mutations, L159M, R166W, and H244R, in the VSX1 gene have been recently reported to be associated with keratoconus by direct sequencing in familial panels. In an attempt to confirm this observation, we surveyed the same mutations of the VSX1 gene for a white sporadic keratoconus case-control panel and a larger familial panel to test its association with keratoconus.
  
  
  METHODS
  A case-control panel, with 77 keratoconus patients and 71 healthy controls, and a keratoconus familial panel, with 444 individuals from 75 families, were surveyed. DNA from each individual was tested for the previously reported mutations by ABI allelic discrimination technology (L159M and R166W) and restriction fragment length polymorphism assay (H244R).
  
  
  RESULTS
  We observed no mutations of R166W and H244R and 1 heterozygous mutation of L159M in a healthy individual in the case-control panel. For the familial panel, we observed no polymorphism of R166W; 3 heterozygous for H244R, with 2 affected and 1 unaffected; and 5 heterozygous for L159M, with 3 affected and 2 unaffected.
  
  
  CONCLUSIONS
  We cannot confirm the previously reported association of the polymorphism in the VSX1 gene with keratoconus. In our case-control sample panel and the larger familial sample panel, we did not observe the reported polymorphism of the VSX1 gene, and the distribution of these 3 polymorphisms was not significant enough to support a pathogenetic role in keratoconus.
authors.affiliation: Cornea Genetic Eye Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Yongming G
authors.initials: YG
authors.lastname: Tang
authors.forename: Yoana
authors.initials: Y
authors.lastname: Picornell
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Su
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Li
authors.forename: Huiying
authors.initials: H
authors.lastname: Yang
authors.forename: Yaron S
authors.initials: YS
authors.lastname: Rabinowitz
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007640:Keratoconus / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; C491583:VSX1 protein, human