title: Novel and recurrent NDP gene mutations in familial cases of Norrie disease and X-linked exudative vitreoretinopathy.
abstract: OBJECTIVE
  To present the results of molecular analysis of the NDP gene in Mexican families with Norrie disease (ND) and X-linked familial exudative vitreoretinopathy (XL-FEVR).
  
  
  METHODS
  Two unrelated families with ND and two with XL-FEVR were studied. Clinical diagnosis was suspected on the basis of a complete ophthalmologic examination. Molecular methods included DNA isolation from peripheral blood leucocytes, polymerase chain reaction amplification and direct nucleotide sequencing analysis of the complete coding region and exon-intron junctions of NDP. Haplotype analysis using NDP-linked microsatellites markers was performed in both ND families.
  
  
  RESULTS
  A novel Norrin missense mutation, p.Arg41Thr, was identified in two apparently unrelated families with ND. Haplotype analysis demonstrated that affected males in these two families shared the same ND-linked haplotype, suggesting a common origin for this novel mutation. The previously reported p.Arg121Trp and p.Arg121Gln Norrin mutations were identified in the two families with XL-FEVR.
  
  
  CONCLUSIONS
  Our results expand the mutational spectrum in ND. This is the first report of ND resulting from mutation at arginine position 41 of Norrin. Interestingly, mutations at the same residue but resulting in a different missense change were previously described in subjects with XL-FEVR (p.Arg41Lys) or persistent fetal vasculature syndrome (p.Arg41Ser), indicating that the novel p.Arg41Thr change causes a more severe retinal phenotype. Preliminary data suggest a founder effect for the ND p.Arg41Thr mutation in these two Mexican families.
authors.affiliation: Research Unit and Department of Genetics, Institute of Ophthalmology Conde de Valenciana, Chimalpopoca 14, Col. Obrera, Mexico City 06800, Mexico.
authors.forename: Erika L
authors.initials: EL
authors.lastname: Pelcastre
authors.forename: Cristina
authors.initials: C
authors.lastname: Villanueva-Mendoza
authors.forename: Juan C
authors.initials: JC
authors.lastname: Zenteno
mesh_terms: D000328:Adult; D001120:Arginine; D001483:Base Sequence; D002675:Child, Preschool; D005122:Exudates and Transudates / Q000378:metabolism*; D005128:Eye Diseases / Q000235:genetics* / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics*; D050172:Genes, X-Linked; D006239:Haplotypes; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D035583:Rare Diseases / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D012008:Recurrence; D012164:Retinal Diseases / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013912:Threonine; D014463:Ultrasonography; D014822:Vitreous Body; D055815:Young Adult
chemical_list: D005136:Eye Proteins; C081848:NDP protein, human; D009419:Nerve Tissue Proteins; D013912:Threonine; D001120:Arginine