Mutation of a nuclear receptor gene, NR2E3 , causes enhanced S cone syndrome, a disorder of retinal cell fate

• Published in: Nature genetics Vol. 24; no. 2; pp. 127 - 131
• Main Authors: Sheffield, Val C, Carmi, Rivka, Hockey, Robin, Haider, Neena B, Searby, Charles, Cideciyan, Artur V, Gorman, Susan, Streb, Luan M, Stone, Edwin M, Wright, Alan F, Hanna, David B, Swiderski, Ruth, Jacobson, Samuel G, Fishman, Gerald A, Bennett, Jean, Duhl, David, Beck, Gretel, Weleber, Richard G
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.02.2000
• Subjects: Amino Acid Sequence; Amino Acid Substitution; Animals; Biological and medical sciences; Chickens; Diagnosis; Drosophila - genetics; enhanced S-cone syndrome; Female; Genetic aspects; Humans; Introns; Male; Medical sciences; Mice; Molecular Sequence Data; Mutation; night blindness; NR2E3 gene; Ophthalmology; Ophthalmoscope and ophthalmoscopy; Orphan Nuclear Receptors; Pedigree; Photoreception; Photoreceptors; PNR gene; Polymorphism, Single-Stranded Conformational; Receptors, Cytoplasmic and Nuclear - genetics; Retina; Retina - metabolism; Retina - pathology; Retina - physiopathology; Retinal Cone Photoreceptor Cells - pathology; Retinal Cone Photoreceptor Cells - physiopathology; Retinal degeneration; Retinal Degeneration - genetics; Retinal Degeneration - pathology; Retinal Degeneration - physiopathology; Retinopathies; Sequence Alignment; Sequence Deletion; Sequence Homology, Amino Acid; Syndrome; Topography; Transcription Factors - genetics; Xenopus laevis; Oregon; United States > US; Illinois; Case study; Human; Eye disease; Nuclear receptor; Retinopathy; Retina; Degenerative disease; Mutation; Transcription factor; Genetic disease
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/72777

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.