<I>NR2E3</I> mutations in enhanced S-cone sensitivity syndrome (ESCS), Goldmann-Favre syndrome (GFS), clumped pigmentary retinal degeneration (CPRD), and retinitis pigmentosa (RP) Export

@article{citeulike:6071706, abstract = {NR2E3, also called photoreceptor-specific nuclear receptor (PNR), is a transcription factor of the nuclear hormone receptor superfamily whose expression is uniquely restricted to photoreceptors. There, its physiological activity is essential for proper rod and cone photoreceptor development and maintenance. Thirty-two different mutations in NR2E3 have been identified in either homozygous or compound heterozygous state in the recessively inherited enhanced S-cone sensitivity syndrome (ESCS), Goldmann-Favre syndrome (GFS), and clumped pigmentary retinal degeneration (CPRD). The clinical phenotype common to all these patients is night blindness, rudimental or absent rod function, and hyperfunction of the ldquobluerdquo S-cones. A single p.G56R mutation is inherited in a dominant manner and causes retinitis pigmentosa (RP). We have established a new locus-specific database for NR2E3 (), containing all reported mutations, polymorphisms, and unclassified sequence variants, including novel ones. A high proportion of mutations are located in the evolutionarily-conserved DNA-binding domains (DBDs) and ligand-binding domains (LBDs) of NR2E3. Based on homology modeling of these NR2E3 domains, we propose a structural localization of mutated residues. The high variability of clinical phenotypes observed in patients affected by NR2E3-linked retinal degenerations may be caused by different disease mechanisms, including absence of DNA-binding, altered interactions with transcriptional coregulators, and differential activity of modifier genes. Hum Mutat 30:1-11, 2009. {\copyright} 2009 Wiley-Liss, Inc.}, address = {Institute for Research in Ophthalmology, Sion, Switzerland; Department of Ophthalmology, University of Lausanne, Lausanne, Switzerland; Ecole Polytechnique F\'{e}d\'{e}rale de Lausanne, Lausanne, Switzerland}, author = {Schorderet, Daniel F. and Escher, Pascal}, citeulike-article-id = {6071706}, citeulike-linkout-0 = {http://dx.doi.org/10.1002/humu.21096}, citeulike-linkout-1 = {http://www3.interscience.wiley.com/cgi-bin/abstract/122519861/ABSTRACT}, doi = {10.1002/humu.21096}, issn = {1098-1004}, journal = {Human Mutation}, keywords = {mir, nr2e3, retina, retinal-dystrophy, retinitis-pigmentosa}, number = {11}, pages = {1475--1485}, posted-at = {2009-11-04 22:40:23}, priority = {2}, title = {<I>NR2E3</I> mutations in enhanced S-cone sensitivity syndrome (ESCS), Goldmann-Favre syndrome (GFS), clumped pigmentary retinal degeneration (CPRD), and retinitis pigmentosa (RP)}, url = {http://dx.doi.org/10.1002/humu.21096}, volume = {30}, year = {2009} }

TY - JOUR ID - citeulike:6071706 L3 - citeulike-article-id:6071706 N2 - NR2E3, also called photoreceptor-specific nuclear receptor (PNR), is a transcription factor of the nuclear hormone receptor superfamily whose expression is uniquely restricted to photoreceptors. There, its physiological activity is essential for proper rod and cone photoreceptor development and maintenance. Thirty-two different mutations in NR2E3 have been identified in either homozygous or compound heterozygous state in the recessively inherited enhanced S-cone sensitivity syndrome (ESCS), Goldmann-Favre syndrome (GFS), and clumped pigmentary retinal degeneration (CPRD). The clinical phenotype common to all these patients is night blindness, rudimental or absent rod function, and hyperfunction of the ldquobluerdquo S-cones. A single p.G56R mutation is inherited in a dominant manner and causes retinitis pigmentosa (RP). We have established a new locus-specific database for NR2E3 (), containing all reported mutations, polymorphisms, and unclassified sequence variants, including novel ones. A high proportion of mutations are located in the evolutionarily-conserved DNA-binding domains (DBDs) and ligand-binding domains (LBDs) of NR2E3. Based on homology modeling of these NR2E3 domains, we propose a structural localization of mutated residues. The high variability of clinical phenotypes observed in patients affected by NR2E3-linked retinal degenerations may be caused by different disease mechanisms, including absence of DNA-binding, altered interactions with transcriptional coregulators, and differential activity of modifier genes. Hum Mutat 30:1-11, 2009. © 2009 Wiley-Liss, Inc. IS - 11 JF - Human Mutation SN - 1098-1004 AD - Institute for Research in Ophthalmology, Sion, Switzerland; Department of Ophthalmology, University of Lausanne, Lausanne, Switzerland; Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland EP - 1485 TI - <I>NR2E3</I> mutations in enhanced S-cone sensitivity syndrome (ESCS), Goldmann-Favre syndrome (GFS), clumped pigmentary retinal degeneration (CPRD), and retinitis pigmentosa (RP) VL - 30 SP - 1475 KW - mir KW - nr2e3 KW - retina KW - retinal-dystrophy KW - retinitis-pigmentosa AU - Schorderet, Daniel AU - Escher, Pascal PY - 2009/// UR - http://dx.doi.org/10.1002/humu.21096 ER -