Recessive NRL mutations in patients with clumped pigmentary retinal degeneration and relative preservation of blue cone function

Koji M. Nishiguchi, James S. Friedman, Michael A. Sandberg, Anand Swaroop, Eliot L. Berson, Thaddeus P. Dryja

Research output: Contribution to journalArticlepeer-review

70 Citations (Scopus)


Mice lacking the transcription factor Nrl have no rod photoreceptors and an increased number of short-wavelength-sensitive cones. Missense mutations in NRL are associated with autosomal dominant retinitis pigmentosa; however, the phenotype associated with the loss of NRL function in humans has not been reported. We identified two siblings who carried two allelic mutations: a predicted null allele (L75fs) and a missense mutation (L160P) altering a highly conserved residue in the domain involved in DNA-binding-site recognition. In vitro luciferase reporter assays demonstrated that the NRL-L160P mutant had severely reduced transcriptional activity compared with the WT NRL protein, consistent with a severe loss of function. The affected patients had night blindness since early childhood, consistent with a severe reduction in rod function. Color vision was normal, suggesting the presence of all cone color types; nevertheless, a comparison of central visual fields evaluated with white-on-white and blue-on-yellow light stimuli was consistent with a relatively enhanced function of short-wavelength-sensitive cones in the macula. The fundi had signs of retinal degeneration (such as vascular attenuation) and clusters of large, clumped, pigment deposits in the peripheral fundus at the level of the retinal pigment epithelium (clumped pigmentary retinal degeneration). Our report presents an unusual clinical phenotype in humans with loss-of-function mutations in NRL.

Original languageEnglish
Pages (from-to)17819-17824
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number51
Publication statusPublished - 2004 Dec 21
Externally publishedYes


  • Cone photoreceptor
  • Retina
  • Retinitis pigmentosa
  • Transcription factor

ASJC Scopus subject areas

  • General


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