Klinische Befunde bei autosomal-rezessivem Syndrom der Blauzapfenhypersensitivität

Jurklies, Bernhard; Weismann, M.; Kellner, Ulrich; Zrenner, Eberhart; Bornfeld, Norbert

doi:10.1007/s003470170164

Cited by 10 publications

(7 citation statements)

References 13 publications

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“…All p.R311Q-patients presented with the symptoms consistently found in recessive NR2E3-linked retinal degenerations as described above. Clumped pigment deposits were shown to involve the macula in one 60-year-old patient, but not in his contemporary first cousin, in line with the previously observed high intrafamilial variability [Jurklies et al, 2001;Pachydaki et al, 2009]. These two patients had no cystoid maculopathy or macular schisis, whereas a 20-yearold patient suffered from cystoid maculopathy, subretinal hemorrhage, and subfoveal neovascularization [Nakamura et al, 2002].…”

Section: Genotype-phenotype Relationshipssupporting

confidence: 73%

“…These symptoms are also present in other retinal degenerations, e.g., congenital stationary night blindness (CSNB; MIM]s 163500, 257270, 300071, 310500, 610427, 610444, and 610445(, fundus albipunctatus (MIM] 136880), retinitis punctata albescens (MIM] 136880), and crystalline corneoretinal Bietti dystrophy (MIM] 210370). However, the ERGs from CSNB patients are different from those affected by ESCS [Jurklies et al, 2001]. In fundus albipunctatus, dark adaptation is markedly prolonged.…”

Section: Differential Diagnosismentioning

confidence: 88%

“…Histological analysis of a postmortem retina from a 77-year-old ESCS patient later confirmed an absence of rods and an increase by approximately two-fold of the number of cones, 92% of which were S-cones [Milam et al, 2002]. Additional clinical findings with an important variability and onset between patients, even inside a same family, including: cystoid maculopathy; retinal degeneration in the region of the vascular arcades, ranging from yellow flecks to clumped or nummular pigment deposition; relative ring scotomas; macular retinoschisis; disorganized retinal lamination; rosette formation in the outer nuclear layer; subfoveal neovascularization; and reduced visual acuity; posterior subcapsular cataracts [Audo et al, 2008;Cideciyan et al, 2003;Greenstein et al, 1996;Jacobson et al, 1990Jacobson et al, , 2004Jurklies et al, 2001;Marmor et al, 1990;Nakamura et al, 2004;Pachydaki et al, 2009;Vaclavik et al, 2008;Yamamoto et al, 1999]. The Goldmann-Favre syndrome (GFS; MIM] 268100) shared several clinical features with ESCS.…”

Section: Introductionmentioning

confidence: 99%

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NR2E3mutations in enhanced S-cone sensitivity syndrome (ESCS), Goldmann-Favre syndrome (GFS), clumped pigmentary retinal degeneration (CPRD), and retinitis pigmentosa (RP)

Schorderet

Escher

2009

Hum. Mutat.

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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. Thirtytwo 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 ''blue'' 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 (www.LOVD.nl/eye), 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.

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Section: Genotype-phenotype Relationshipssupporting

confidence: 73%

Section: Differential Diagnosismentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

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NR2E3mutations in enhanced S-cone sensitivity syndrome (ESCS), Goldmann-Favre syndrome (GFS), clumped pigmentary retinal degeneration (CPRD), and retinitis pigmentosa (RP)

Schorderet

Escher

2009

Hum. Mutat.

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“…In a proband without NR2E3 mutation (Patient A), the following retinal function studies were specifically performed: static threshold perimetry in the dark-adapted (500-and 650-nm stimuli) and light-adapted (600-nm stimulus on 2.7 log td white background; 440-nm stimulus on a 4.0 log td yellow background) states using a modified automated perimeter, to determine the retinal sensitivities to light of different wavelengths (Humphrey Field Analyzer, San Leandro, CA); full-field electroretinography (ERG) to determine the electrical responses of the retina to light ; and cross-sectional retinal imaging with optical coherence tomography (OCT3, Zeiss Humphrey Instruments, Dublin, CA). The methods used to characterize phenotype were those used in our previous studies of ESCS-NR2E3 Roman and Jacobson, 1991;Kellner et al, 1993;Hood et al, 1995;Haider et al, 2000;Jurklies et al, 2001;Milam et al, 2002;Cideciyan et al, 2003). Informed consent for all procedures was obtained from subjects after the nature of the studies had been explained.…”

Section: Clinical Studiesmentioning

confidence: 99%

Mutation analysis ofNR2E3 andNRL genes in Enhanced S Cone Syndrome

et al. 2004

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Ten new and seventeen previously reported Enhanced S Cone Syndrome (ESCS) subjects were used to search for genetic heterogeneity. All subjects were diagnosed with ESCS on the basis of clinical, psychophysical and/or electroretinography testing using published criteria. Mutation analysis was performed on the NR2E3 nuclear receptor gene by single strand conformation analysis and direct sequencing, which revealed either homozygous (N=13) or compound heterozygous (N=11) mutations in 24 subjects (89%), heterozygous mutations in 2 subjects (7%) and no mutations in 1 subject (4%). Fifteen different mutations were identified, including six not previously reported. The subject (Patient A) with no detected NR2E3 mutation had features not usually associated with ESCS, in particular moderate rod photoreceptor function in peripheral retina and an abnormally thick retinal nerve fibre layer. Mutation analysis of the NRL, CRX, NR1D1 and THRB genes in this individual revealed a heterozygous one base-pair insertion in exon 2 of the NRL gene, which results in a predicted truncation of the NRL protein. Loss-of-function NRL alleles have not been described previously in humans, but since the same mutation was present in unaffected family members, it raises the possibility that the abnormal ESCS phenotype in Patient A may result from a digenic mechanism, with a heterozygous NRL mutation and a mutation in another unknown gene.

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“…It is characterized by night blindness, cystoid maculopathy and degenerative changes of the vascular arcades (Marmor 1989; Jacobson et al 1990, 1991; Marmor et al 1990; Roman & Jacobson 1991). Patients with ESCS have been reported worldwide, including in Japan (Kellner et al 1993; Yamamoto et al 1999; Jurklies et al 2001; Nakamura et al 2002). Full‐field and spectral electroretinographic findings have shown that while patients with ESCS have severely reduced responses of the rods, 30‐Hz flicker, and middle (M) and long wavelength‐sensitive (L) cones, they have hypersensitive responses of the S‐cones (Jacobson et al 1990; Marmor et al 1990; Hood et al 1995; Greenstein et al 1996).…”

Section: Introductionmentioning

confidence: 99%

Enhanced S‐cone syndrome in a Japanese family with a nonsense NR2E3 mutation (Q350X)

Nakamura

Hayashi

Kozaki

et al. 2004

Acta Ophthalmologica Scandinavica

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ABSTRACT.Purpose: To describe the clinical characteristics of a Japanese male patient with enhanced S-cone syndrome (ESCS) and investigate the existence of mutations in the NR2E3 gene, which encodes a photoreceptor cell-specific nuclear receptor. Methods: Fundus examinations, fluorescein angiography, colour vision tests, spectral sensitivity, and full-field and spectral electroretinography were performed. Mutation screening of the NR2E3 gene was performed with polymerase chain reaction (PCR) amplification and direct sequencing. Results: We identified a novel homozygous mutation (c.1048C > T), that converts glutamine (CAA) to a termination codon (TAA) at amino acid position 350. The subject's unaffected parents were heterozygous for the mutation, consistent with autosomal recessive transmission. The electroretinographic findings revealed that the patient had neither rod nor 30-Hz flicker responses but did have cone responses with large a-wave and low b-wave amplitudes, similar to the rod-plus-cone responses, and also substantial short wavelength-sensitive (S) cone and extremely diminished long/middle wavelength-sensitive (L/M) cone responses. In the right eye, spectral sensitivity in the fovea revealed both functional S-cone and remarkably reduced L-and M-cone sensitivities, which was compatible with the decreased visual acuity (VA) and red/green colour vision defects noted in this eye. In contrast, the patient had good VA and normal red/green colour vision in the left eye. Conclusion: The nonsense mutation results in a truncated NR2E3 protein lacking 61 amino acids within the ligand-binding domain (LBD) that consists of 190 amino acids of the C-terminus end. Therefore, null function of the LBD is likely to cause ESCS in the patient. The clinical findings for this patient suggest that his left eye, with its functional L/M-and S-cones, was at an earlier stage of the syndrome than his right eye.

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Klinische Befunde bei autosomal-rezessivem Syndrom der Blauzapfenhypersensitivität

Cited by 10 publications

References 13 publications

NR2E3mutations in enhanced S-cone sensitivity syndrome (ESCS), Goldmann-Favre syndrome (GFS), clumped pigmentary retinal degeneration (CPRD), and retinitis pigmentosa (RP)

NR2E3mutations in enhanced S-cone sensitivity syndrome (ESCS), Goldmann-Favre syndrome (GFS), clumped pigmentary retinal degeneration (CPRD), and retinitis pigmentosa (RP)

Mutation analysis ofNR2E3 andNRL genes in Enhanced S Cone Syndrome

Enhanced S‐cone syndrome in a Japanese family with a nonsense NR2E3 mutation (Q350X)

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