title: 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.
authors.affiliation: Howard Hughes Medical Institute, University of Iowa, Iowa City, Iowa, USA.
authors.forename: N B
authors.initials: NB
authors.lastname: Haider
authors.forename: S G
authors.initials: SG
authors.lastname: Jacobson
authors.forename: A V
authors.initials: AV
authors.lastname: Cideciyan
authors.forename: R
authors.initials: R
authors.lastname: Swiderski
authors.forename: L M
authors.initials: LM
authors.lastname: Streb
authors.forename: C
authors.initials: C
authors.lastname: Searby
authors.forename: G
authors.initials: G
authors.lastname: Beck
authors.forename: R
authors.initials: R
authors.lastname: Hockey
authors.forename: D B
authors.initials: DB
authors.lastname: Hanna
authors.forename: S
authors.initials: S
authors.lastname: Gorman
authors.forename: D
authors.initials: D
authors.lastname: Duhl
authors.forename: R
authors.initials: R
authors.lastname: Carmi
authors.forename: J
authors.initials: J
authors.lastname: Bennett
authors.forename: R G
authors.initials: RG
authors.lastname: Weleber
authors.forename: G A
authors.initials: GA
authors.lastname: Fishman
authors.forename: A F
authors.initials: AF
authors.lastname: Wright
authors.forename: E M
authors.initials: EM
authors.lastname: Stone
authors.forename: V C
authors.initials: VC
authors.lastname: Sheffield
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D002645:Chickens; D004330:Drosophila / Q000235:genetics; D005260:Female; D006801:Humans; D007438:Introns; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D057093:Orphan Nuclear Receptors; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D012160:Retina / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology / Q000503:physiopathology*; D012162:Retinal Degeneration / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D016415:Sequence Alignment; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*; D014982:Xenopus laevis
chemical_list: C403073:NR2E3 protein, human; C485736:Nr2e3 protein, mouse; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors