title: Familial cases of Norrie disease detected by copy number analysis.
abstract: OBJECTIVE
  Norrie disease (ND, MIM#310600) is an X-linked disorder characterized by severe vitreoretinal dysplasia at birth. We report the results of causative NDP gene analysis in three male siblings with Norrie disease and describe the associated phenotypes.
  
  
  METHODS
  Three brothers with suspected Norrie disease and their mother presented for clinical examination. After obtaining informed consent, DNA was extracted from the peripheral blood of the proband, one of his brothers and his unaffected mother. Exons 1-3 of the NDP gene were amplified by polymerase chain reaction (PCR), and direct sequencing was performed. Multiplex ligation-dependent probe amplification (MLPA) was also performed to search for copy number variants in the NDP gene.
  
  
  RESULTS
  The clinical findings of the three brothers included no light perception, corneal opacity, shallow anterior chamber, leukocoria, total retinal detachment and mental retardation. Exon 2 of the NDP gene was not amplified in the proband and one brother, even when the PCR primers for exon 2 were changed, whereas the other two exons showed no mutations by direct sequencing. MLPA analysis showed deletion of exon 2 of the NDP gene in the proband and one brother, while there was only one copy of exon 2 in the mother.
  
  
  CONCLUSIONS
  Norrie disease was diagnosed in three patients from a Japanese family by clinical examination and was confirmed by genetic analysis. To localize the defect, confirmation of copy number variation by the MLPA method was useful in the present study.
authors.affiliation: Department of Ophthalmology, Juntendo University Graduate School of Medicine, 3-1-3 Hongo, Bunkyo-ku, Tokyo, 113-8431, Japan, eiarai27@gmail.com.
authors.forename: Eisuke
authors.initials: E
authors.lastname: Arai
authors.forename: Takuro
authors.initials: T
authors.lastname: Fujimaki
authors.forename: Ai
authors.initials: A
authors.lastname: Yanagawa
authors.forename: Keiko
authors.initials: K
authors.lastname: Fujiki
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Akihisa
authors.initials: A
authors.lastname: Okumura
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shimizu
authors.forename: Akira
authors.initials: A
authors.lastname: Murakami
mesh_terms: D000293:Adolescent; D001766:Blindness / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics; D002648:Child; D056915:DNA Copy Number Variations / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D005784:Gene Amplification; D040181:Genetic Diseases, X-Linked; D006801:Humans; D008297:Male; D060885:Multiplex Polymerase Chain Reaction; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009422:Nervous System Diseases / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012162:Retinal Degeneration; D035781:Siblings; D013036:Spasms, Infantile / Q000175:diagnosis / Q000235:genetics*
chemical_list: D005136:Eye Proteins; C081848:NDP protein, human; D009419:Nerve Tissue Proteins