title: Genotype-phenotype variations in five Spanish families with Norrie disease or X-linked FEVR.
abstract: OBJECTIVE
  Norrie disease (OMIM 310600) is a rare X-linked disorder characterized by congenital blindness in males. Approximately 40 to 50% of the cases develop deafness and mental retardation. X-linked familial exudative vitreoretinopathy (XL-FEVR) is a hereditary ocular disorder characterized by a failure of peripheral retinal vascularization. Both X-linked disorders are due to mutations in the NDP gene, which encodes a 133 amino acid protein called Norrin, but autosomal recessive (AR) and autosomal dominant (AD) forms of FEVR have also been described. In this study, we report the molecular findings and the related phenotype in five Spanish families affected with Norrie disease or XL-FEVR due to mutations of the NDP gene.
  
  
  METHODS
  The study was conducted in 45 subjects from five Spanish families. These families were clinically diagnosed with Norrie disease or similar conditions. The three exons of the NDP gene were analyzed by automatic DNA sequencing. Haplotype analyses were also performed.
  
  
  RESULTS
  Two new nonsense mutations, apart from other mutations previously described in the NDP gene, were found in those patients affected with ND or X-linked FEVR.
  
  
  CONCLUSIONS
  An important genotype-phenotype variation was found in relation to the different mutations of the NDP gene. In fact, the same mutation may be responsible for different phenotypes. We speculate that there might be other molecular factors that interact in the retina with Norrin, which contribute to the resultant phenotypes.
authors.affiliation: Department of Genetics, Fundacion Jimenez Diaz, Madrid, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Riveiro-Alvarez
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Trujillo-Tiebas
authors.forename: Ascension
authors.initials: A
authors.lastname: Gimenez-Pardo
authors.forename: Maria
authors.initials: M
authors.lastname: Garcia-Hoyos
authors.forename: Diego
authors.initials: D
authors.lastname: Cantalapiedra
authors.forename: Isabel
authors.initials: I
authors.lastname: Lorda-Sanchez
authors.forename: Marta
authors.initials: M
authors.lastname: Rodriguez de Alba
authors.forename: Carmen
authors.initials: C
authors.lastname: Ramos
authors.forename: Carmen
authors.initials: C
authors.lastname: Ayuso
mesh_terms: D000293:Adolescent; D001766:Blindness / Q000151:congenital*; D002675:Child, Preschool; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D003638:Deafness / Q000235:genetics; D005122:Exudates and Transudates; D005128:Eye Diseases / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D015792:Retinal Dysplasia / Q000235:genetics*; D013030:Spain; D014822:Vitreous Body
chemical_list: D018389:Codon, Nonsense; D005136:Eye Proteins; C081848:NDP protein, human; D009419:Nerve Tissue Proteins