title: Genetic screening of Wnt signaling factors in advanced retinopathy of prematurity.
abstract: OBJECTIVE
  To evaluate the possibility of genetic involvement in retinopathy of prematurity (ROP). Although ROP is most often associated with low birthweight and low gestational age, these factors do not necessarily predict the severity of ROP. The possible involvement of other factors, including genetic variants, has been considered. Familial exudative vitreoretinopathy (FEVR) is a hereditary vitreoretinal disorder with clinical manifestations similar to those of ROP. Three genes involving the wingless/int1 (Wnt) receptor signaling pathway-FZD4 for frizzled 4, LRP5 for low-density lipoprotein receptor-related protein 5, and ND for Norrie disease protein-are associated with the development of FEVR.
  
  
  METHODS
  In the present study, 17 Japanese patients with advanced ROP were screened for these three candidate genes of FEVR. Genomic DNA from each patient was subjected to PCR and direct sequencing of the ND, FZD4, and LRP5 genes.
  
  
  RESULTS
  One patient had a heterozygous mutation in the 5' untranslated region of the ND gene. Another had a leucine insertion in the signal peptide of LRP5. None showed any mutation in FZD4.
  
  
  CONCLUSIONS
  These findings suggest that genetic changes in the Wnt receptor signaling pathway associate to the development of advanced ROP.
authors.affiliation: Department of Ophthalmology, Nippon Medical School, Tokyo, Japan. mikihira@nms.ac.jp
authors.forename: Miki
authors.initials: M
authors.lastname: Hiraoka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Hideo
authors.initials: H
authors.lastname: Orimo
authors.forename: Miina
authors.initials: M
authors.lastname: Hiraoka
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ogata
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Azuma
mesh_terms: D001483:Base Sequence; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics; D012178:Retinopathy of Prematurity / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D005136:Eye Proteins; C081848:NDP protein, human; D009419:Nerve Tissue Proteins; D051153:Wnt Proteins