title: Molecular analysis of the VSX1 gene in familial keratoconus.
abstract: OBJECTIVE
  To evaluate the role of the visual system homeobox gene 1 (VSX1) in the pathogenesis of familial keratoconus.
  
  
  METHODS
  Families with two or more individuals with keratoconus were recruited and their members examined. The coding region and intron-exon junctions of the VSX1 gene were sequenced in affected individuals. In cases where there were possible pathogenic changes, segregation within the pedigree was analyzed. Meta analysis of reports on an association of p.D144E change with keratoconus phenotype was performed.
  
  
  RESULTS
  Probands from a panel of 85 apparently unrelated keratoconus families were included. Eleven sequence variants were observed, including the previously reported c.432C>G (p.D144E) change and two novel intronic single nucleotide polymorphisms. However, these three changes did not cosegregate with the disease phenotype.
  
  
  CONCLUSIONS
  We excluded the c.432C>G sequence alteration as the direct cause of the disease. Lack of possibly pathogenic VSX1 sequence variants in the familial panel suggests that involvement of this gene in the pathogenesis of keratoconus is likely to be confined to a small number of pedigrees, at least in the population studied.
authors.affiliation: Division of Molecular Genetics, Institute of Ophthalmology, UCL, London, UK. p.liskova@ucl.ac.uk
authors.forename: Petra
authors.initials: P
authors.lastname: Liskova
authors.forename: Neil D
authors.initials: ND
authors.lastname: Ebenezer
authors.forename: Pirro G
authors.initials: PG
authors.lastname: Hysi
authors.forename: Rhian
authors.initials: R
authors.lastname: Gwilliam
authors.forename: Mohamed F
authors.initials: MF
authors.lastname: El-Ashry
authors.forename: Lalitha C
authors.initials: LC
authors.lastname: Moodaley
authors.forename: Scott
authors.initials: S
authors.lastname: Hau
authors.forename: Michael
authors.initials: M
authors.lastname: Twa
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Tuft
authors.forename: Shomi S
authors.initials: SS
authors.lastname: Bhatacharya
mesh_terms: D000328:Adult; D001224:Aspartic Acid; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D018698:Glutamic Acid; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007640:Keratoconus / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; C491583:VSX1 protein, human; D001224:Aspartic Acid; D018698:Glutamic Acid