Abstract：
BACKGROUND: 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.
METHODS: 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).
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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).
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：视网膜色素变性（RP），导致视力逐渐丧失的异质性遗传性视网膜疾病，影响全球100多万人。CNGA1和CNGB1基因的致病变异，分别占病例的1%和4%，影响杆状感光细胞中的环核苷酸门控通道。这项研究的目的是描述和比较一组与CNGA1或CNGB1相关的RP患者的基因型和临床特征，并探索潜在的基因型-表型相关性。
方法：以下数据来自CNGA1或CNGB1相关RP患者，紧随其后的是五次意大利继承的视网膜变性服务，回顾性收集：CNGA1和CNGB1的遗传变异，最佳矫正视力（BCVA），椭球区(EZ)宽度,眼底照片和短波长眼底自发荧光（SW-AF）图像。通过首先根据负责疾病的基因将队列分成两组(CNGA1和CNGB1组)进行比较和相关性分析。并行,整个RP患者队列分为另外两组，根据蛋白质水平变体的预期影响（低组和高组）。
结果：总计，招募了29名患者，11与CNGA1-和18与CNGB1相关的RP。在CNGA1和CNGB1中均发现了5种新的CNGA1变体和5种新的CNGB1变体。BCVA在CNGA1和CNGB1组之间具有可比性，以及低群体和高群体之间。CNGA1组的平均EZ宽度大于CNGB1组，尽管没有统计学意义，而EZ宽度在低和高组之间没有差异在整个RP患者队列中观察到EZ宽度与BCVA之间以及EZ宽度与年龄之间的统计学显着相关性。队列中所有患者的眼底照片显示经典RP模式，在SW-AF图像中，有14/21例患者观察到高自发荧光环。
结论：在CNGA1和CNGB1相关形式中，棒CNG通道相关RP被证明是一种缓慢进展的疾病，使其成为基因增强疗法的理想候选者。
方法：以下数据来自CNGA1或CNGB1相关RP患者，紧随其后的是五次意大利继承的视网膜变性服务，回顾性收集：CNGA1和CNGB1的遗传变异，最佳矫正视力（BCVA），椭球区(EZ)宽度,眼底照片和短波长眼底自发荧光（SW-AF）图像。通过首先根据负责疾病的基因将队列分成两组(CNGA1和CNGB1组)进行比较和相关性分析。并行,整个RP患者队列分为另外两组，根据蛋白质水平变体的预期影响（低组和高组）。
结果：总计，招募了29名患者，11与CNGA1-和18与CNGB1相关的RP。在CNGA1和CNGB1中均发现了5种新的CNGA1变体和5种新的CNGB1变体。BCVA在CNGA1和CNGB1组之间具有可比性，以及低群体和高群体之间。CNGA1组的平均EZ宽度大于CNGB1组，尽管没有统计学意义，而EZ宽度在低和高组之间没有差异在整个RP患者队列中观察到EZ宽度与BCVA之间以及EZ宽度与年龄之间的统计学显着相关性。队列中所有患者的眼底照片显示经典RP模式，在SW-AF图像中，有14/21例患者观察到高自发荧光环。
结论：在CNGA1和CNGB1相关形式中，棒CNG通道相关RP被证明是一种缓慢进展的疾病，使其成为基因增强疗法的理想候选者。
