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

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.