title: Developmental or degenerative--NR2E3 gene mutations in two patients with enhanced S cone syndrome.
abstract: OBJECTIVE
  Enhanced S Cone Syndrome is a rare autosomal recessive disorder characterized clinically by an absence of rod function, a replacement of most L and M cone function by S cone activity (Goldmann-Favre Syndrome) and by variable degrees of retinal degeneration in different families. The causative gene, nuclear receptor subfamily 2, group E, member 3 (NR2E3), controls the developmental sequence for rods and cones. The purpose of this study was to compare the nature and implications of mutations in two subjects with Enhanced S Cone Syndrome who have significantly different degrees of degenerative damage.
  
  
  METHODS
  A direct sequencing approach was used to identify the mutations. Genomic DNA was amplified from all the exons of NR2E3 and used as a template for sequencing. Of the two families studied, Case 1 is of Persian ethnicity while Case 2 is Brazilian. A total of six individuals within the two families were studied.
  
  
  RESULTS
  Case 1 (original propositus of the syndrome) has the characteristic developmental rod/cone abnormality with large amplitude electroretinogram responses and no retinal degeneration. She was homozygous for a novel mutation, c.[del196-201del6] (p.G66-C67del), which lies entirely within the P-box for this gene. By comparison, Case 2 had Goldmann-Favre Syndrome with retinal degeneration and low electroretinogram signals. She was a compound heterozygote for c.[119-2A>C]+[del194-202del9] (p.N65-C67del), mutations that have been reported previously. Her second mutation overlaps that of Case 1 within the P-box.
  
  
  CONCLUSIONS
  The novel in-frame homozygous deletion of Case 1, within the P-box motif of the DNA binding domain, caused a developmental abnormality without retinal degeneration. Case 2, with more traditional Goldmann-Favre Syndrome with retinal degeneration, was a compound heterozygote where one allele had a similar P-box deletion but the other was a splicing defect. Case 1 is the first reported homozygous deletion within the P-box. This is the first report of NR2E3 mutations in a Persian and a Brazilian family.
authors.affiliation: Department of Ophthalmology, University of California Irvine, Irvine, CA, USA.
authors.forename: Nitin
authors.initials: N
authors.lastname: Udar
authors.forename: Kent
authors.initials: K
authors.lastname: Small
authors.forename: Meenal
authors.initials: M
authors.lastname: Chalukya
authors.forename: Rosamaria
authors.initials: R
authors.lastname: Silva-Garcia
authors.forename: Michael
authors.initials: M
authors.lastname: Marmor
mesh_terms: D000328:Adult; D001483:Base Sequence; D002648:Child; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D007438:Introns / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D057093:Orphan Nuclear Receptors / Q000235:genetics*; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology*; D012162:Retinal Degeneration / Q000235:genetics* / Q000503:physiopathology; D013577:Syndrome
chemical_list: C403073:NR2E3 protein, human; D057093:Orphan Nuclear Receptors