Mutation of a nuclear receptor gene, NR2E3, causes enhanced S cone syndrome, a disorder of retinal cell fate
Abstract
Hereditary human retinal degenerative diseases usually affect the mature photoreceptor topography by reducing the number of cells through apoptosis, resulting in loss of visual function. Only one inherited retinal disease, the enhanced S-cone syndrome (ESCS), manifests a gain in function of photoreceptors. ESCS is an autosomal recessive retinopathy in which patients have an increased sensitivity to blue light; perception of blue light is mediated by what is normally the least populous cone photoreceptor subtype, the S (short wavelength, blue) cones. People with ESCS also suffer visual loss, with night blindness occurring from early in life, varying degrees of L (long, red)- and M (middle, green)-cone vision, and retinal degeneration. The altered ratio of S- to L/M-cone photoreceptor sensitivity in ESCS may be due to abnormal cone cell fate determination during retinal development. In 94% of a cohort of ESCS probands we found mutations in NR2E3 (also known as PNR), which encodes a retinal nuclear receptor recently discovered to be a ligand-dependent transcription factor. Expression of NR2E3 was limited to the outer nuclear layer of the human retina. Our results suggest that NR2E3 has a role in determining photoreceptor phenotype during human retinogenesis.
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The retinal degeneration 7 mouse has a mutation in the Nr2e3 gene responsible for Goldmann Favre disease, or human enhanced S-cone syndrome (ESCS).
“The retinal degeneration 7 mouse has a mutation in the Nr2e3 gene responsible for Goldmann Favre disease, or human enhanced S-cone syndrome (ESCS)”
From Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD) (2010) · cites this paper as Haider et al., 2000
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- Authors
- Haider, N. B., Jacobson, S. G., Cideciyan, A. V., Swiderski, R., Streb, L. M., Searby, C., Beck, G., Hockey, R., Hanna, D. B., Gorman, S., Duhl, D., Carmi, R., Bennett, J., Weleber, R. G., Fishman, G. A., Wright, A. F., Stone, E. M., & Sheffield, V. C.
- Affiliations
- University of Iowa (US)
- University of Pennsylvania (US)
- Howard Hughes Medical Institute (US)
- Ben-Gurion University of the Negev (IL)
- Oregon Health & Science University (US)
- University of Illinois Chicago (US)
- Western General Hospital (GB)
- Corresponding author
- Sheffield, Val C.
- ORCID
- Venue
- Nature Genetics
- Published
- 2000-02
- Volume
- 24
- Issue
- 2
- Pages
- 127-131
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W1968703962
- Cited by
- 507
- References
- 28
- Citations by year
- 2026: 14 · 2025: 22 · 2024: 16 · 2023: 13 · 2022: 16 · 2021: 19 · 2020: 17 · 2019: 19 · 2018: 12 · 2017: 19 · 2016: 19 · 2015: 18 · 2014: 17 · 2013: 17 · 2012: 22
- FWCI
- 6.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ey005627-16)
- National Eye Institute (R01EY011298, R01EY010539, EY-05627, EY-11298, EY10539)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Ocular Disorders and Treatments
- Keywords
- enhanced S-cone syndrome, NR2E3, PNR, nuclear receptors, retinal development, S-cone photoreceptors, blue light sensitivity, night blindness, retinal degeneration, gain-of-function mutations
- MeSH terms
- Amino Acid Sequence, Animals, Chickens, Drosophila, Female, Humans, Introns, Male, Molecular Sequence Data, Mutation, Pedigree, Retina, Retinal Degeneration, Syndrome, Transcription Factors, Xenopus laevis, Sequence Alignment, Sequence Deletion, Sequence Homology, Amino Acid, Retinal Cone Photoreceptor Cells, Receptors, Cytoplasmic and Nuclear, Polymorphism, Single-Stranded Conformational, Amino Acid Substitution, Mice, Orphan Nuclear Receptors
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