Atypical mild enhanced S-Cone syndrome with novel compound heterozygosity of the NR2E3 gene

PURPOSE: To report mild enhanced s-cone syndrome (ESCS) associated with a novel heterozygous mutation of the NR2E3 gene. DESIGN: Observational case report. METHODS: Clinical examination, optical coherence tomography (OCT), electroretinography (ERG), genetic analysis, and protein homology modeling. RESULTS: Examination of a 9,year-old girl with acute visual loss of the left eye showed visual acuity of 20/30 in the right eye and 20/200 in the left eye; OCT revealed a choroidal neovascular membrane (CNVM) in the left fovea and cystic maculopathy in the right eye. Full,field ERG showed supranormal s-cone responses, reduced rod response, and characteristic ESCS waveform in photopic cone response but not in scotopic bright,flash response. Sequence analysis revealed heterozygous mutations in the NR2E3 gene, c.767C -> T yielding a substitution p.Ala256Val, and a mutation in the splice site before exon 2, c. 119-2 A -> C. CONCLUSIONS: The p.Ala256Val mutation affects the ligand binding domain of the NR2E3 nuclear receptor only, resulting in modestly impaired ESCS ERG results.