title: Phenotypic heterogeneity associated with a novel mutation (Gly112Glu) in the Norrie disease protein.
abstract: OBJECTIVE
  To determine the molecular pathology and clinical severity of two pedigrees with a history of early retinal detachment and peripheral retinal vascular abnormalities.
  
  
  METHODS
  Longitudinal cohort study.
  
  
  METHODS
  A longitudinal clinical study and DNA analysis was performed on 49 family members of two pedigrees.
  
  
  RESULTS
  Nine individuals were found to be hemizygous for a mutation at codon 112 (Gly112Glu) of the Norrie disease protein (NDP) in one pedigree. Significant phenotypic heterogeneity was found. The proband presented with a unilateral subtotal retinal detachment at the age of 3 years, and subsequently developed a slowly progressive tractional retinal detachment involving the macula in the contralateral eye at the age of 4 years. One individual had only mild peripheral retinal pigmentary changes with normal vision at the age of 79 years. The remaining seven individuals had varying degrees of peripheral retinal vascular abnormalities and anterior segment findings. Seven affected members of a second pedigree affected by a previously reported mutation, Arg74Cys, also demonstrated wide ocular phenotypic variation.
  
  
  CONCLUSIONS
  A novel mutation (Gly112Glu), which represents the most carboxy located, NDP mutation reported, results in significant phenotypic heterogeneity. These data support the contention that the spectrum of ocular disease severity associated with these NDP mutations is broad. Use of terms that characterize this entity by phenotypic appearance, such as familial exudative vitreoretinopathy, do not adequately communicate the potential spectrum of severity of this disorder to affected or carrier family members.
authors.affiliation: Molecular Ophthalmology Laboratory, Center for Macular Degeneration, The University of Iowa Carver School of Medicine, Iowa City, IA 52242, USA.
authors.forename: R C
authors.initials: RC
authors.lastname: Allen
authors.forename: S R
authors.initials: SR
authors.lastname: Russell
authors.forename: L M
authors.initials: LM
authors.lastname: Streb
authors.forename: A
authors.initials: A
authors.lastname: Alsheikheh
authors.forename: E M
authors.initials: EM
authors.lastname: Stone
mesh_terms: D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D015785:Eye Diseases, Hereditary / Q000235:genetics* / Q000503:physiopathology; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012163:Retinal Detachment / Q000235:genetics* / Q000503:physiopathology; D012171:Retinal Vessels / Q000002:abnormalities*
chemical_list: D005136:Eye Proteins; C081848:NDP protein, human; D009419:Nerve Tissue Proteins