Background/aims To investigate genotype–phenotype associations in patients with KCNV2 retinopathy. Methods Review of clinical notes, best-corrected visual acuity (BCVA), molecular variants, electroretinography (ERG) and retinal imaging. Subjects were grouped according to the combination of KCNV2 variants—two loss-of-function (TLOF), two missense (TM) or one of each (MLOF)—and parameters were compared. Results Ninety-two patients were included. The mean age of onset (mean±SD) in TLOF (n=55), TM (n=23) and MLOF (n=14) groups was 3.51±0.58, 4.07±2.76 and 5.54±3.38 years, respectively. The mean LogMAR BCVA (±SD) at baseline in TLOF, TM and MLOF groups was 0.89±0.25, 0.67±0.38 and 0.81±0.35 for right, and 0.88±0.26, 0.69±0.33 and 0.78±0.33 for left eyes, respectively. The difference in BCVA between groups at baseline was significant in right (p=0.03) and left eyes (p=0.035). Mean outer nuclear layer thickness (±SD) at baseline in TLOF, MLOF and TM groups was 37.07±15.20 µm, 40.67±12.53 and 40.38±18.67, respectively, which was not significantly different (p=0.85). The mean ellipsoid zone width (EZW) loss (±SD) was 2051 µm (±1318) for patients in the TLOF, and 1314 µm (±965) for MLOF. Only one patient in the TM group had EZW loss at presentation. There was considerable overlap in ERG findings, although the largest DA 10 ERG b-waves were associated with TLOF and the smallest with TM variants. Conclusions Patients with missense alterations had better BCVA and greater structural integrity. This is important for patient prognostication and counselling, as well as stratification for future gene therapy trials. Data sharing not applicable as no datasets generated and/or analysed for this study.

中文翻译：

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KCNV2 相关视网膜病变：基因型-表型相关性 – KCNV2 研究组报告 3


背景/目的 调查 KCNV2 视网膜病变患者的基因型-表型关联。方法 回顾临床记录、最佳矫正视力 (BCVA)、分子变异、视网膜电图 (ERG) 和视网膜成像。根据 KCNV2 变异的组合（两个功能丧失 (TLOF)、两个错义 (TM) 或各一个 (MLOF)）对受试者进行分组，并比较参数。结果 纳入 92 名患者。 TLOF (n=55)、TM (n=23) 和 MLOF (n=14) 组的平均发病年龄 (mean±SD) 分别为 3.51±0.58、4.07±2.76 和 5.54±3.38 岁。 TLOF、TM 和 MLOF 组基线时的平均 LogMAR BCVA (±SD) 右眼分别为 0.89±0.25、0.67±0.38 和 0.81±0.35，左眼分别为 0.88±0.26、0.69±0.33 和 0.78±0.33。基线时各组之间的 BCVA 差异在右眼 (p=0.03) 和左眼 (p=0.035) 中显着。 TLOF、MLOF和TM组基线时的平均外核层厚度（±SD）分别为37.07±15.20μm、40.67±12.53和40.38±18.67，没有显着差异（p=0.85）。 TLOF 患者的平均椭球区宽度 (EZW) 损失 (±SD) 为 2051μm (±1318)，MLOF 患者的平均椭球区宽度 (EZW) 损失 (±SD) 为 1314μm (±965)。 TM 组中只有一名患者就诊时出现 EZW 丢失。尽管最大的 DA 10 ERG b 波与 TLOF 相关，最小的 DA 10 ERG b 波与 TM 变异相关，但 ERG 结果存在相当大的重叠。结论 存在错义改变的患者具有更好的 BCVA 和更高的结构完整性。这对于患者预测和咨询以及未来基因治疗试验的分层非常重要。数据共享不适用，因为本研究没有生成和/或分析数据集。