A novel mutation (Cys83Tyr) in the second zinc finger of NR2E3 in enhanced S-cone syndrome.
BACKGROUND
Enhanced S-cone syndrome (ESCS) is an autosomal recessive retinal disorder characterized by an increased number of S-cones over L/M cones and rods. Mutations in the NR2E3 gene, encoding a photoreceptor-specific nuclear receptor, are identified in patients with ESCS. The purpose of this study is to report the ophthalmic features of a 25-year-old Portuguese male with a typical ESCS phenotype and a novel homozygous NR2E3 mutation.


METHODS
The patient underwent a detailed ophthalmic examination including fundus photography, fluorescein angiography (FAF), fundus autofluorescence imaging (FAI), and spectral domain optical coherence tomography (SD-OCT). Full-field electroretinography (ERG), S-cone ERG, and multifocal ERG were performed. Mutation screening of the NR2E3 gene was performed with polymerase chain reaction amplification and direct sequencing.


RESULTS
The patient had poor visual acuity but good color vision. Funduscopy showed degenerative changes from the vascular arcades to the midperipheral retina. The SD-OCT revealed macular schisis and cystoid changes that had no fluorescein leakage. The posterior pole showed diffusely increased autofluorescence compared with eccentric areas in both eyes. International-standard full-field ERG showed the typical pathognomonic changes associated with ESCS and the short-wavelength flash ERG was simplified, delayed, and similar to the standard photopic flash ERG. Multifocal ERG showed widespread delay and reduction. Genetic analysis revealed a novel homozygous mutation (p.C83Y), which resides in the second zinc finger of the DNA-binding domain.


CONCLUSIONS
This homozygous mutation is likely to affect binding to target DNA sites, resulting in a non-functional behavior of NR2E3 protein. It is associated with a typical form of ESCS with a nondetectable rod response and reduced/delayed mfERG responses at all eccentricities.
Rocha-Sousa
Amândio
A
Department of Ophthalmology, Hospital de São João, Porto, Portugal. arsousa@med.up.pt
Hayashi
Takaaki
T
Gomes
Nuno Lourenço
NL
Penas
Susana
S
Brandão
Elisete
E
Rocha
Paulo
P
Urashima
Mitsuyoshi
M
Yamada
Hisashi
H
Tsuneoka
Hiroshi
H
Falcão-Reis
Fernando
F
D000328:Adult; D055358:Cone Opsins / Q000235:genetics*; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005091:Exons / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D005451:Fluorescein Angiography; D006801:Humans; D008297:Male; D057093:Orphan Nuclear Receptors / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology*; D012162:Retinal Degeneration / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D013577:Syndrome; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology; D058609:Visual Field Tests; D014794:Visual Fields; D016335:Zinc Fingers / Q000235:genetics*
D055358:Cone Opsins; D005136:Eye Proteins; C403073:NR2E3 protein, human; D057093:Orphan Nuclear Receptors