Novel NR2E3 Mutations (R104Q, R334G) Associated with a Mild Form of Enhanced S-Cone Syndrome Demonstrate Compound Heterozygosity

Hayashi, Takaaki; Gekka, Tamaki; Goto-Omoto, Satoshi; Takeuchi, Tomokazu; Kubo, Akiko; Kono, Kenji

doi:10.1016/j.ophtha.2005.07.002

Cited by 35 publications

(29 citation statements)

References 24 publications

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“…Atypical ESCS has been reported in which S-cone responses are enhanced, but, unusually, variable degrees of preserved rod responses were evident on ERG. 23,27,49 In 2 of these families, compound heterozygous NR2E3 mutations were found in association with a milder phenotype, but molecular screening was negative in a third family. The NR2E3 protein constitutes a DNA-binding domain (DBD) (amino acid residues 45-131) and a ligand-binding domain (LBD) (amino acid residues 222-410).…”

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confidence: 99%

Clinical and Molecular Characterization of Enhanced S-Cone Syndrome in Children

et al. 2014

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IMPORTANCE Enhanced S-cone syndrome (ESCS) forms part of the differential diagnosis of night blindness in childhood.OBJECTIVE To report in detail the clinical phenotype and molecular genetic findings in a series of children with ESCS.DESIGN, SETTING AND PARTICIPANTS Nine children with ESCS from 5 families underwent full ophthalmic examination, electrophysiological testing, and retinal imaging at a genetic eye disease clinic of a tertiary referral eye hospital. Bidirectional Sanger sequencing of all exons and intron-exon boundaries of NR2E3 was performed. MAIN OUTCOMES AND MEASURESResults of ophthalmic examination and sequence analysis of NR2E3. RESULTS In total, 5 girls and 4 boys with a diagnosis of ESCS were included in the study. All patients had developed nyctalopia from early childhood. Visual acuity ranged from 0.00 to 1.20 logMAR (20/20 to 20/320 Snellen). All patients had hyperopia. Three patients had nummular pigmentary lesions along the arcades as typically seen in adults, 4 patients had mild pigmentary disturbance or white dots along the arcades, and 2 patients had a normal retinal appearance, although their fundus autofluorescence imaging demonstrated foci of increased autofluorescence along the arcades. Three patients had macular schisis-like changes on optical coherence tomography. Eight patients had electrophysiological testing at a mean age of 8.6 years (age range, 3-14 years), and in each patient the findings were consistent with the diagnosis of ESCS. Direct sequencing of NR2E3 identified 3 previously described mutations and 4 novel mutations. Seven patients were compound heterozygous for mutations in NR2E3, and 2 additional sibling patients were presumed to be homozygous for a missense change based on parental sequencing. CONCLUSIONS AND RELEVANCEIn this sample, children with ESCS had an early onset of night blindness and hyperopia but no nystagmus. Based on this study, children with ESCS may initially manifest a normal fundus appearance but later develop mottled retinal pigment epithelium change along the arcades, followed by the appearance of white dots in the same distribution. Fundus autofluorescence imaging is abnormal in children with a normal fundus appearance. The electrophysiological findings are pathognomonic and allow targeted molecular screening and a specific diagnosis.

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confidence: 99%

Clinical and Molecular Characterization of Enhanced S-Cone Syndrome in Children

et al. 2014

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“…The hypersensitivity of S-cones in ESCS is due to a greater number of S-cones than the more normally abundant L or M-cones (Hood et al, 1995). In humans, different mutations in NR2E3 have been correlated with ESCS (Haider et al, 2000, Hayashi et al, 2005, Milam et al, 2002, Nakamura et al, 2002, Nakamura et al, 2004, Sharon et al, 2003, Wright et al, 2004, although mutations in NRL have also been correlated with ESCS (Wright et al, 2004). In many of the cases where the NR2E3 gene is mutated, an increased number of S-cones, retinal dysplasia and degeneration was observed (Haider et al, 2000).…”

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confidence: 99%

The Xenopus ortholog of the nuclear hormone receptor Nr2e3 is primarily expressed in developing photoreceptors

Luna¹,

El‐Hodiri²

2007

Int. J. Dev. Biol.

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Nr2e3 is a nuclear hormone receptor that is involved in rod photoreceptor differentiation. The Nr2e3 gene was previously identified in humans, mice, zebrafish and chicken. In all species, Nr2e3 expression is restricted to the retina and is believed to have a role in rod photoreceptor specification and maintenance. Here we report the identification and characterization of the Xenopus Nr2e3. We found that Nr2e3 is primarily expressed in developing rod photoreceptors. In contrast to other species, Nr2e3 is also expressed in the notochord and pineal gland during Xenopus laevis development.

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“…Genetic analysis was performed at the Department of Ophthalmology at The Jikei University as previously described [12,15]. Briefly, genomic DNA was extracted from venous blood samples using a Puregene Blood DNA Isolation kit (Gentra Systems, Minneapolis, MN).…”

Section: Molecular Genetic Studiesmentioning

confidence: 99%

“…Briefly, genomic DNA was extracted from venous blood samples using a Puregene Blood DNA Isolation kit (Gentra Systems, Minneapolis, MN). For mutation screening, all exons (exon 1 to exon 8) and the promoter region of the NR2E3 gene were amplified by polymerase chain reaction (PCR) using previously reported primers [12,15]. The PCR products were purified with a QIAquick PCR Purification kit (Qiagen, Tokyo, Japan) and used as the template for sequencing.…”

Section: Molecular Genetic Studiesmentioning

confidence: 99%

“…Functionally, NR2E3 protein regulates the proper differentiation and maturation of rod and cone photoreceptors [6][7][8][9][10]. To date, more than 30 mutations in the NR2E3 gene have been described not only in ESCS [4,[11][12][13][14][15] but also in GoldmannFavre syndrome (GFS) [11,16], autosomal recessive retinitis pigmentosa [17,18], autosomal dominant retinitis pigmentosa [17,19], and clumped pigmentary retinal degeneration [11]. Because appropriate ERG analyses demonstrated a relatively enhanced S-cone function and the presence of NR2E3 mutations in GFS, it was concluded that the two diseases are likely to be one clinical entity, being the GFS the severe phenotype [11,16,20].…”

Section: Introductionmentioning

confidence: 99%

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