Recurrent mutation in the first zinc finger of the orphan nuclear receptor NR2E3 causes autosomal dominant retinitis pigmentosa

Am J Hum Genet. 2007 Jul;81(1):147-57. doi: 10.1086/518426. Epub 2007 May 24.


"Autosomal dominant retinitis pigmentosa" (adRP) refers to a genetically heterogeneous group of retinal dystrophies, in which 54% of all cases can be attributed to 17 disease loci. Here, we describe the localization and identification of the photoreceptor cell-specific nuclear receptor gene NR2E3 as a novel disease locus and gene for adRP. A heterozygous mutation c.166G-->A (p.Gly56Arg) was identified in the first zinc finger of NR2E3 in a large Belgian family affected with adRP. Overall, this missense mutation was found in 3 families affected with adRP among 87 unrelated families with potentially dominant retinal dystrophies (3.4%), of which 47 were affected with RP (6.4%). Interestingly, affected members of these families display a novel recognizable NR2E3-related clinical subtype of adRP. Other mutations of NR2E3 have previously been shown to cause autosomal recessive enhanced S-cone syndrome, a specific retinal phenotype. We propose a different pathogenetic mechanism for these distinct dominant and recessive phenotypes, which may be attributed to the dual key role of NR2E3 in the regulation of photoreceptor-specific genes during rod development and maintenance.

MeSH terms

  • Amino Acid Sequence
  • Belgium
  • Chromosome Mapping
  • Female
  • Genes, Dominant*
  • Heterozygote
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation, Missense
  • Orphan Nuclear Receptors
  • Pedigree
  • Receptors, Cytoplasmic and Nuclear / chemistry
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Retinitis Pigmentosa / genetics*
  • Retinitis Pigmentosa / pathology
  • Transcription Factors / chemistry
  • Transcription Factors / genetics*
  • Zinc Fingers / genetics*


  • NR2E3 protein, human
  • Orphan Nuclear Receptors
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors