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Novel NR2E3 mutations (R104Q, R334G) associated with a mild form of enhanced S-cone syndrome demonstrate compound heterozygosity.
Ophthalmology. 2005 Dec; 112(12):2115.O

Abstract

PURPOSE

We investigated the ophthalmic features of a mild form of enhanced S-cone syndrome (ESCS) in a 33-year-old Japanese female proband and 3 unaffected family members. A genetic analysis was performed.

DESIGN

Genetic and observational case study.

METHODS

Fundus examinations, optical coherence tomography (OCT), Goldmann visual field (VF) perimetry, color vision tests, spectral sensitivity, and full-field and spectral electroretinography (ERG) were performed. Mutation screening of the NR2E3 gene, which encodes a photoreceptor-specific orphan nuclear receptor, was performed with polymerase chain reaction amplification and direct sequencing.

MAIN OUTCOME MEASURES

Mutations in the NR2E3 gene, fundus photographs, OCT images, VFs, spectral sensitivity, and ERG findings.

RESULTS

The diagnosis of ESCS was made based on the distinctive spectral ERG findings: hypersensitivity to blue stimuli and hyposensitivity to red stimuli. The proband had good visual acuity, normal color vision, good central VFs, and nearly normal spectral sensitivity. Funduscopy showed degenerative lesions in the vascular arcades to the midperipheral retina. The OCT images showed a morphologically normal macular thickness. In the full-field ERG, low amplitudes of rod b-waves were detected. Waveforms between rod-plus-cone and cone ERGs were very similar. Mutation analysis identified 2 novel compound heterozygous missense mutations, p.R104Q and p.R334G, which reside in the DNA-binding domain (DBD) and ligand-binding domain (LBD), respectively. The unaffected parents carried one of these mutations each, consistent with autosomal recessive transmission.

CONCLUSIONS

Our study suggests that the expression of these 2 mutants of NR2E3, acting as a dimer, is correlated with a mild form of ESCS in that full foveal function and retinal laminar structure are maintained, and certain rod responses are present. This may be explained by the possibility that the heterodimers encoded by the 2 mutant alleles retain certain NR2E3 functions through the respective intact DBD and LBD.

Authors+Show Affiliations

Department of Ophthalmology, Jikei University School of Medicine, Tokyo, Japan. taka@jikei.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16225923

Citation

Hayashi, Takaaki, et al. "Novel NR2E3 Mutations (R104Q, R334G) Associated With a Mild Form of Enhanced S-cone Syndrome Demonstrate Compound Heterozygosity." Ophthalmology, vol. 112, no. 12, 2005, p. 2115.
Hayashi T, Gekka T, Goto-Omoto S, et al. Novel NR2E3 mutations (R104Q, R334G) associated with a mild form of enhanced S-cone syndrome demonstrate compound heterozygosity. Ophthalmology. 2005;112(12):2115.
Hayashi, T., Gekka, T., Goto-Omoto, S., Takeuchi, T., Kubo, A., & Kitahara, K. (2005). Novel NR2E3 mutations (R104Q, R334G) associated with a mild form of enhanced S-cone syndrome demonstrate compound heterozygosity. Ophthalmology, 112(12), 2115.
Hayashi T, et al. Novel NR2E3 Mutations (R104Q, R334G) Associated With a Mild Form of Enhanced S-cone Syndrome Demonstrate Compound Heterozygosity. Ophthalmology. 2005;112(12):2115. PubMed PMID: 16225923.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel NR2E3 mutations (R104Q, R334G) associated with a mild form of enhanced S-cone syndrome demonstrate compound heterozygosity. AU - Hayashi,Takaaki, AU - Gekka,Tamaki, AU - Goto-Omoto,Satoshi, AU - Takeuchi,Tomokazu, AU - Kubo,Akiko, AU - Kitahara,Kenji, Y1 - 2005/10/12/ PY - 2005/05/22/received PY - 2005/07/04/accepted PY - 2005/10/18/pubmed PY - 2005/12/15/medline PY - 2005/10/18/entrez SP - 2115 EP - 2115 JF - Ophthalmology JO - Ophthalmology VL - 112 IS - 12 N2 - PURPOSE: We investigated the ophthalmic features of a mild form of enhanced S-cone syndrome (ESCS) in a 33-year-old Japanese female proband and 3 unaffected family members. A genetic analysis was performed. DESIGN: Genetic and observational case study. METHODS: Fundus examinations, optical coherence tomography (OCT), Goldmann visual field (VF) perimetry, color vision tests, spectral sensitivity, and full-field and spectral electroretinography (ERG) were performed. Mutation screening of the NR2E3 gene, which encodes a photoreceptor-specific orphan nuclear receptor, was performed with polymerase chain reaction amplification and direct sequencing. MAIN OUTCOME MEASURES: Mutations in the NR2E3 gene, fundus photographs, OCT images, VFs, spectral sensitivity, and ERG findings. RESULTS: The diagnosis of ESCS was made based on the distinctive spectral ERG findings: hypersensitivity to blue stimuli and hyposensitivity to red stimuli. The proband had good visual acuity, normal color vision, good central VFs, and nearly normal spectral sensitivity. Funduscopy showed degenerative lesions in the vascular arcades to the midperipheral retina. The OCT images showed a morphologically normal macular thickness. In the full-field ERG, low amplitudes of rod b-waves were detected. Waveforms between rod-plus-cone and cone ERGs were very similar. Mutation analysis identified 2 novel compound heterozygous missense mutations, p.R104Q and p.R334G, which reside in the DNA-binding domain (DBD) and ligand-binding domain (LBD), respectively. The unaffected parents carried one of these mutations each, consistent with autosomal recessive transmission. CONCLUSIONS: Our study suggests that the expression of these 2 mutants of NR2E3, acting as a dimer, is correlated with a mild form of ESCS in that full foveal function and retinal laminar structure are maintained, and certain rod responses are present. This may be explained by the possibility that the heterodimers encoded by the 2 mutant alleles retain certain NR2E3 functions through the respective intact DBD and LBD. SN - 1549-4713 UR - https://www.unboundmedicine.com/medline/citation/16225923/Novel_NR2E3_mutations__R104Q_R334G__associated_with_a_mild_form_of_enhanced_S_cone_syndrome_demonstrate_compound_heterozygosity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0161-6420(05)00894-8 DB - PRIME DP - Unbound Medicine ER -