No VSX1 gene mutations associated with keratoconus

Invest Ophthalmol Vis Sci. 2006 Jul;47(7):2820-2. doi: 10.1167/iovs.05-1530.

Abstract

Purpose: To determine whether mutations of the VSX1 gene play a pathogenetic role in the development of keratoconus (KTCN).

Methods: DNA extraction, PCR amplification, and direct sequencing of the VSX1 gene were performed in 100 unrelated patients with diagnoses of clinical and topographic features of KTCN.

Results: Of the four previously identified presumed pathogenic mutations in the VSX1 gene (Leu17Pro, Asp144Glu, Leu159Met, and Arg166Trp), only Asp144Glu was identified in a single affected patient. Two novel single nucleotide polymorphisms (SNPs), both resulting in synonymous substitutions, were identified: c.53G>T (Ser6Ser) in four affected patients and c.209G>T (Pro58Pro) in two affected patients. Two previously reported SNPs were also identified: c.426C>A (Arg131Ser) in one affected patient and c.581A>G (Ala182Ala) in 51 of the 100 affected patients.

Conclusions: Only one of the presumed pathogenic mutations in the VSX1 gene, Asp144Glu, was identified in a single member of the cohort of affected patients. However, as previously demonstrated, Asp144Glu is a non-disease-causing polymorphism. The absence of pathogenic mutations in the VSX1 gene in a large number of unrelated KTCN patients indicates that other genetic factors are involved in the development of this disorder.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • DNA Mutational Analysis
  • Eye Proteins / genetics*
  • Female
  • Homeodomain Proteins / genetics*
  • Humans
  • Keratoconus / genetics*
  • Keratoconus / surgery
  • Keratoplasty, Penetrating
  • Male
  • Middle Aged
  • Mutation*
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide

Substances

  • Eye Proteins
  • Homeodomain Proteins
  • VSX1 protein, human