Abstract：
Enhanced S-cone syndrome (ESCS) is a rare autosomal recessive retinal degeneration mainly associated with pathogenic variations in the NR2E3 gene. Only a few pathogenic variations in the NRL gene associated with ESCS have been reported to date. Here, we describe the clinical and genetic findings of two unrelated pediatric patients with a novel frameshift homozygous variant in the NRL gene. Fundus examinations showed signs of peripheral degeneration in both patients, more severe in Proband 2, with relative sparing of the macular area. Spectral domain optical coherence tomography (SD-OCT) revealed a significant macular involvement with cysts in Proband 1, and minimal foveal alteration with peripheral retina involvement in Proband 2. Visual acuity was abnormal in both patients, but more severely affected in Proband 1 than Proband 2. The electroretinogram recordings showed reduced scotopic, mixed and single flash cone responses, with a typical supernormal S-cone response, meeting the criteria for a clinical diagnosis of ESCS in both patients. The present report expands the clinical and genetic spectrum of NRL-associated ESCS, and confirms the age-independent variability of phenotypic presentation already described in the NR2E3-associated ESCS.
摘要：
增强型S-锥综合征（ESCS）是一种罕见的常染色体隐性视网膜变性，主要与NR2E3基因的致病变异有关。迄今为止，仅报道了与ESCS相关的NRL基因中的少数致病性变异。这里,我们描述了两名在NRL基因中具有新型移码纯合变体的无关儿科患者的临床和遗传学发现.眼底检查显示两名患者均有外周变性的迹象，在Proband2中更为严重，黄斑区相对较少。谱域光学相干断层扫描（SD-OCT）显示，在Proband1中，黄斑明显受累于囊肿，在Proband2中，中央凹改变与周围视网膜受累最小。两名患者的视力异常，但在Proband1中比Proband2受影响更严重。视网膜电图记录显示暗视减少，混合和单闪光锥响应，具有典型的超常S锥反应，符合ESCS的临床诊断标准。本报告扩展了NRL相关ESCS的临床和遗传谱，并证实了NR2E3相关ESCS中已经描述的表型呈现的年龄依赖性变异性。
