title: Norrie disease gene sequence variants in an ethnically diverse population with retinopathy of prematurity.
abstract: OBJECTIVE
  Retinopathy of prematurity (ROP) is a leading cause of visual loss in the pediatric population. Mutations in the Norrie disease gene (NDP) are associated with heritable retinal vascular disorders, and have been found in a small subset of patients with severe retinopathy of prematurity. Varying rates of progression to threshold disease in different races may have a genetic basis, as recent studies suggest that the incidence of NDP mutations may vary in different groups. African Americans, for example, are less likely to develop severe degrees of ROP. We screened a large cohort of ethnically diverse patients for mutations in the entire NDP.
  
  
  METHODS
  A total of 143 subjects of different ethnic backgrounds were enrolled in the study. Fifty-four patients had severe ROP (Stage 3 or worse). Of these, 38 were threshold in at least one eye (with a mean gestational age of 26.1 weeks and mean birth weight of 788.4 g). There were 36 patients with mild or no ROP, 31 parents with no history of retinal disease or prematurity, and 22 wild type (normal) controls. There were 70 African American subjects, 55 Caucasians, and 18 of other races. Severe ROP was noted in 29 African American subjects, 17 Caucasians, and 8 of other races. Seven polymerase chain reaction primer pairs spanning the NDP were optimized for denaturing high performance liquid chromatography and direct sequencing. Three primer pairs covered the coding region, and the remaining four spanned the 3' and 5' untranslated regions (UTR).
  
  
  RESULTS
  Six of 54 (11%) infants with severe ROP had polymorphisms in the NDP. Five of the infants were African American, and one was Caucasian. Two parents were heterozygous for the same polymorphism as their child. One parent-child pair had a single base pair (bp) insertion in the 3' UTR region. Another parent-child pair had two mutations: a 14 bp deletion in the 5' UTR region of exon 1 and a single nucleotide polymorphism in the 5' UTR region of exon 2. No coding region sequence changes were found. No polymorphisms were observed in infants with mild or no ROP, or in the wild type controls.
  
  
  CONCLUSIONS
  Of the six sequence alterations found, five were novel nucleotide changes: One in the 5' UTR region of exon 2, and four in the 3' UTR region of exon 3. The extent of NDP polymorphisms in this large, racially diverse group of infants is moderate. NDP polymorphisms may play a role in the pathogenesis of ROP, but do not appear to be a major causative factor.
authors.affiliation: Department of Ophthalmology, Children's National Medical Center, Washington, DC, USA.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Hutcheson
authors.forename: Prasuna C
authors.initials: PC
authors.lastname: Paluru
authors.forename: Steven L
authors.initials: SL
authors.lastname: Bernstein
authors.forename: Jamie
authors.initials: J
authors.lastname: Koh
authors.forename: Eric F
authors.initials: EF
authors.lastname: Rappaport
authors.forename: Richard A
authors.initials: RA
authors.lastname: Leach
authors.forename: Terri L
authors.initials: TL
authors.lastname: Young
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D020121:5' Untranslated Regions / Q000235:genetics; D000328:Adult; D001741:Black or African American / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D004251:DNA Transposable Elements; D005091:Exons; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012178:Retinopathy of Prematurity / Q000208:ethnology* / Q000235:genetics* / Q000503:physiopathology; D012720:Severity of Illness Index; D044465:White People / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D004251:DNA Transposable Elements; D005136:Eye Proteins; C081848:NDP protein, human; D009419:Nerve Tissue Proteins