A NR2E3 Mutation (R309G) Associated With a Mild Form of Enhanced S-Cone Syndrome

GALANTUOMO, MARIA SILVANA;ZUCCA, IGNAZIO ALBERTO;S. BANFI;C. ZIVIELLO;G. CARBONI;G. FORMA;Y. TITI;FOSSARELLO, MAURIZIO

2008-01-01

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Abstract

Purpose: We investigated the ophthalmic features of a mild form of enhanced S-cone syndrome (ESCS) in a 9-year-old Sardinian female proband and 3 unaffected family members. A genetic analysis was performed. Methods: Fundus examinations (fundus photography, fluorescein angiography and fundus autofluorescence (AF), optical coherence tomography (OCT), automatic perimetry (AP) (W/W and B/Y), color vision tests, 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 using an integrated strategy including the use of a microarray chip (available at Asperbio) that allows the screening of a large number of mutations already known to be responsible for autosomal recessive RP and direct sequencing analysis. Results: The diagnosis of ESCS was made based on the distinctive visual field (B/Y vs. W/W) and spectral ERG findings: hypersensitivity to blue stimuli and hyposensitivity to red stimuli. The proband had good visual acuity, normal color vision, good central VFs (B/Y better than W/W). Funduscopy showed pigment clumpings from the vascular arcades to the midperipheral retina. Fundus AF imaging revealed a wide disciform area of hyper-autofluorescence located in the macula. The OCT images showed a morphologically normal macular thickness in LE, and abnormal macular thickness related to cystoid edema in RE, which was responsive to oral acetazolamide. 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 a homozigous mutation, R309G, which resides in the ligand-binding domain (LBD). The unaffected parents carried one of these mutations each, consistent with autosomal recessive transmission. Conclusions: Our study suggests that the expression of this mutant of NR2E3, 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.