Department of Ophthalmology, ASST Santi Paolo e Carlo Hospital, University of Milan, Milan, Italy.
MAGI'S LAB S.R.L., Rovereto, Italy.
Ophthalmic Res. 2024;67(1):301-310. doi: 10.1159/000538746. Epub 2024 May 7.
Retinitis pigmentosa (RP), a heterogeneous inherited retinal disorder causing gradual vision loss, affects over 1 million people worldwide. Pathogenic variants in CNGA1 and CNGB1 genes, respectively, accounting for 1% and 4% of cases, impact the cyclic nucleotide-gated channel in rod photoreceptor cells. The aim of this study was to describe and compare genotypic and clinical characteristics of a cohort of patients with CNGA1- or CNGB1-related RP and to explore potential genotype-phenotype correlations.
The following data from patients with CNGA1- or CNGB1-related RP, followed in five Italian inherited retinal degenerations services, were retrospectively collected: genetic variants in CNGA1 and CNGB1, best-corrected visual acuity (BCVA), ellipsoid zone (EZ) width, fundus photographs, and short-wavelength fundus autofluorescence (SW-AF) images. Comparisons and correlation analyses were performed by first dividing the cohort in two groups according to the gene responsible for the disease (CNGA1 and CNGB1 groups). In parallel, the whole cohort of RP patients was divided into two other groups, according to the expected impact of the variants at protein level (low and high group).
In total, 29 patients were recruited, 11 with CNGA1- and 18 with CNGB1-related RP. In both CNGA1 and CNGB1, 5 novel variants in CNGA1 and 5 in CNGB1 were found. BCVA was comparable between CNGA1 and CNGB1 groups, as well as between low and high groups. CNGA1 group had a larger mean EZ width compared to CNGB1 group, albeit not statistically significant, while EZ width did not differ between low and high groups A statistically significant correlation between EZ width and BCVA as well as between EZ width and age were observed in the whole cohort of RP patients. Fundus photographs of all patients in the cohort showed classic RP pattern, and in SW-AF images an hyperautofluorescent ring was observed in 14/21 patients.
Rod CNG channel-associated RP was demonstrated to be a slowly progressive disease in both CNGA1- and CNGB1-related forms, making it an ideal candidate for gene augmentation therapies.
色素性视网膜炎（RP）是一种异质性遗传性视网膜疾病，可导致视力逐渐丧失，影响全球超过 100 万人。CNGA1 和 CNGB1 基因的致病性变异分别占病例的 1%和 4%，影响视杆细胞中的环核苷酸门控通道。本研究旨在描述和比较携带 CNGA1 或 CNGB1 相关 RP 的患者的基因型和临床特征，并探讨潜在的基因型-表型相关性。
回顾性收集了在意大利 5 个遗传性视网膜退行性疾病服务中心接受治疗的 CNGA1 或 CNGB1 相关 RP 患者的数据：CNGA1 和 CNGB1 中的遗传变异、最佳矫正视力（BCVA）、椭圆体带（EZ）宽度、眼底照片和短波眼底自发荧光（SW-AF）图像。首先根据导致疾病的基因（CNGA1 和 CNGB1 组）将队列分为两组，然后进行比较和相关性分析。同时，根据变异蛋白水平的预期影响（低和高组），将整个 RP 患者队列分为两组。
共纳入 29 例患者，其中 11 例为 CNGA1 相关，18 例为 CNGB1 相关。在 CNGA1 和 CNGB1 中，发现了 5 个 CNGA1 中的新变异和 5 个 CNGB1 中的新变异。CNGA1 组和 CNGB1 组之间的 BCVA 无显著差异，低组和高组之间的 BCVA 也无显著差异。尽管 CNGA1 组的平均 EZ 宽度大于 CNGB1 组，但无统计学意义，而低组和高组之间的 EZ 宽度无统计学差异。在整个 RP 患者队列中，观察到 EZ 宽度与 BCVA 之间以及 EZ 宽度与年龄之间存在显著相关性。该队列的所有患者的眼底照片均显示出典型的 RP 模式，在 21 例患者中的 14 例中观察到 SW-AF 图像中的高自发荧光环。
在 CNGA1 和 CNGB1 相关形式中，杆状 CNG 通道相关的 RP 被证明是一种缓慢进展的疾病，使其成为基因增强治疗的理想候选者。
