title: Novel mutations in Norrie disease gene in Japanese patients with Norrie disease and familial exudative vitreoretinopathy.
abstract: OBJECTIVE
  To search for mutations in the Norrie disease gene (NDP) in Japanese patients with familial exudative vitreoretinopathy (FEVR) and Norrie disease (ND) and to delineate the mutation-associated clinical features.
  
  
  METHODS
  Direct sequencing after polymerase chain reaction of all exons of the NDP gene was performed on blood collected from 62 probands (31 familial and 31 simplex) with FEVR, from 3 probands with ND, and from some of their family members. The clinical symptoms and signs in the patients with mutations were assessed. X-inactivation in the female carriers was examined in three FEVR families by using leukocyte DNA.
  
  
  RESULTS
  Four novel mutations-I18K, K54N, R115L, and IVS2-1G-->A-and one reported mutation, R97P, in the NDP gene were identified in six families. The severity of vitreoretinopathy varied among these patients. Three probands with either K54N or R115L had typical features of FEVR, whereas the proband with R97P had those of ND. Families with IVS2-1G-->A exhibited either ND or FEVR characteristics. A proband with I18K presented with significant phenotypic heterogeneity between the two eyes. In addition, affected female carriers in a family harboring the K54N mutation presented with different degrees of vascular abnormalities in the periphery of the retina. X-inactivation profiles indicated that the skewing was not significantly different between affected and unaffected women.
  
  
  CONCLUSIONS
  These observations indicate that mutations of the NDP gene can cause ND and 6% of FEVR cases in the Japanese population. The X-inactivation assay with leukocytes may not be predictive of the presence of a mutation in affected female carriers.
authors.affiliation: Department of Ophthalmology, Fukuoka University School of Medicine, Fukuoka, Japan. hkondo@fukuoka-u.ac.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kondo
authors.forename: Minghui
authors.initials: M
authors.lastname: Qin
authors.forename: Shunji
authors.initials: S
authors.lastname: Kusaka
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tahira
authors.forename: Haruyuki
authors.initials: H
authors.lastname: Hasebe
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Eiichi
authors.initials: E
authors.lastname: Uchio
authors.forename: Kenshi
authors.initials: K
authors.lastname: Hayashi
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000208:ethnology; D001766:Blindness / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D041321:Chromosomes, Human, X / Q000235:genetics; D004252:DNA Mutational Analysis; D003638:Deafness / Q000208:ethnology / Q000235:genetics / Q000473:pathology; D005122:Exudates and Transudates; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000208:ethnology / Q000235:genetics / Q000473:pathology; D007564:Japan / Q000453:epidemiology; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012164:Retinal Diseases / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D018630:Vitreoretinopathy, Proliferative / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D049951:X Chromosome Inactivation / Q000235:genetics
chemical_list: D005136:Eye Proteins; C081848:NDP protein, human; D009419:Nerve Tissue Proteins