A mutation in NRL is associated with autosomal dominant retinitis pigmentosa

Bessant, David; Payne, Annette; Mitton, Kenneth P; Wang, Qingliang; Swain, Prabodha K.; Plant, Catherine; Bird, Alan C.; Zack, Donald J.; Swaroop, Anand; Bhattacharya, Siladitya

doi:10.1038/7678

Cited by 192 publications

(88 citation statements)

References 13 publications

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“…Mutations in NRL have been described in patients with autosomal dominant RP and autosomal recessive CPRD. 38,39 In patient 32666, a homozygous missense mutation was identified that substitutes a serine for an arginine residue For each mutation, the predicted effect on the protein level is presented. For multiplex families, the number of affected individuals who also carry the mutation homozygously is presented.…”

Section: Nr2e3mentioning

confidence: 99%

High-Resolution Homozygosity Mapping Is a Powerful Tool to Detect Novel Mutations Causative of Autosomal Recessive RP in the Dutch Population

Collin

Born

Klevering

et al. 2011

Invest. Ophthalmol. Vis. Sci.

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Section: Nr2e3mentioning

confidence: 99%

High-Resolution Homozygosity Mapping Is a Powerful Tool to Detect Novel Mutations Causative of Autosomal Recessive RP in the Dutch Population

Collin

Born

Klevering

et al. 2011

Invest. Ophthalmol. Vis. Sci.

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“…5 Humans with mutations in NRL have autosomal dominant retinitis pigmentosa, and electroretinography reveals a severe loss of both rod and cone function. 4,57 It is tempting then to compare the S-cone function of Nrl Ϫ/Ϫ mouse retina with patients with enhanced short-wave cone syndrome (ESCS) who have missense mutations in the NR2E3 gene, but have less severe degeneration of cone function and an increased ratio of S-cones to L/M-cones (i.e., ESCS). 58 -61 However, there are important differences in the consequences of NR2E3 defects and deletion of Nrl in mice.…”

Section: Mutations or Deletions In Nr2e3 Enhanced Short-wave Cone Symentioning

confidence: 99%

“…[1][2][3] Missense mutations in NRL are associated with autosomal dominant retinitis pigmentosa in humans. 4 Deletion of Nrl in mice (Nrl Ϫ/Ϫ ) results in the complete absence of rods in the retina, as revealed by histology, immunocytochemistry, electrophysiology, and gene expression analysis. Instead, there is a concomitant increase in short-wave-sensitive photoreceptor cells, apparently generated by switching of rod to cone cell fate during development.…”

mentioning

confidence: 99%

Cone-like Morphological, Molecular, and Electrophysiological Features of the Photoreceptors of theNrlKnockout Mouse

Daniele

Lillo

Lyubarsky

et al. 2005

Invest. Ophthalmol. Vis. Sci.

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“…Nrl appears to be a molecular switch between cone and rod cell fate: if a photoreceptor precursor expresses Nrl it becomes a rod, otherwise it becomes a cone [21]. All three genes have been implicated in a variety of blinding diseases in humans [14], [22], [23]. Previous studies of mice with mutations in these TFs identified a range of potential target genes [9], [18], [20], [24], [25].…”

Section: Introductionmentioning

confidence: 99%

The Cis-regulatory Logic of the Mammalian Photoreceptor Transcriptional Network

et al. 2007

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The photoreceptor cells of the retina are subject to a greater number of genetic diseases than any other cell type in the human body. The majority of more than 120 cloned human blindness genes are highly expressed in photoreceptors. In order to establish an integrative framework in which to understand these diseases, we have undertaken an experimental and computational analysis of the network controlled by the mammalian photoreceptor transcription factors, Crx, Nrl, and Nr2e3. Using microarray and in situ hybridization datasets we have produced a model of this network which contains over 600 genes, including numerous retinal disease loci as well as previously uncharacterized photoreceptor transcription factors. To elucidate the connectivity of this network, we devised a computational algorithm to identify the photoreceptor-specific cis-regulatory elements (CREs) mediating the interactions between these transcription factors and their target genes. In vivo validation of our computational predictions resulted in the discovery of 19 novel photoreceptor-specific CREs near retinal disease genes. Examination of these CREs permitted the definition of a simple cis-regulatory grammar rule associated with high-level expression. To test the generality of this rule, we used an expanded form of it as a selection filter to evolve photoreceptor CREs from random DNA sequences in silico. When fused to fluorescent reporters, these evolved CREs drove strong, photoreceptor-specific expression in vivo. This study represents the first systematic identification and in vivo validation of CREs in a mammalian neuronal cell type and lays the groundwork for a systems biology of photoreceptor transcriptional regulation.

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A mutation in NRL is associated with autosomal dominant retinitis pigmentosa

Cited by 192 publications

References 13 publications

High-Resolution Homozygosity Mapping Is a Powerful Tool to Detect Novel Mutations Causative of Autosomal Recessive RP in the Dutch Population

High-Resolution Homozygosity Mapping Is a Powerful Tool to Detect Novel Mutations Causative of Autosomal Recessive RP in the Dutch Population

Cone-like Morphological, Molecular, and Electrophysiological Features of the Photoreceptors of theNrlKnockout Mouse

The Cis-regulatory Logic of the Mammalian Photoreceptor Transcriptional Network

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