Genotypic and Phenotypic Characterization of a Cohort of Patients Affected by Rod Cyclic Nucleotide Channel-Associated Retinitis Pigmentosa.

IF 2 4区医学 Q2 OPHTHALMOLOGY

Ophthalmic Research Pub Date : 2024-01-01 Epub Date: 2024-05-07 DOI:10.1159/000538746

Leonardo Colombo, Gabriele Bonetti, Paolo Enrico Maltese, Giancarlo Iarossi, Lucia Ziccardi, Paolo Fogagnolo, Valentino De Ruvo, Vittoria Murro, Dario Giorgio, Benedetto Falsini, Giorgio Placidi, Salvatore Martella, Eleonora Galantin, Matteo Bertelli, Luca Rossetti

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引用次数: 0

Abstract

Introduction: 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.

Conclusion: 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.

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杆状 CNG 通道相关视网膜色素变性患者群体的基因型和表型特征。

前言视网膜色素变性（RP）是一种异质性遗传性视网膜疾病，会导致视力逐渐减退，全球有超过 100 万人受其影响。CNGA1 和 CNGB1 基因的致病变异影响杆状感光细胞中的环核苷酸门控通道，分别占病例的 1%和 4%。本研究旨在描述和比较一组 CNGA1 或 CNGB1 相关 RP 患者的基因型和临床特征，并探讨潜在的基因型与表型之间的相关性：回顾性收集了意大利五家遗传性视网膜变性服务机构随访的 CNGA1- 或 CNGB1 相关 RP 患者的以下数据：CNGA1 和 CNGB1 基因变异、最佳矫正视力 (BCVA)、椭圆带 (EZ) 宽度、眼底照片和短波长眼底自动荧光 (SW-AF) 图像。首先根据致病基因将样本分为两组（CNGA1 组和 CNGB1 组），然后进行比较和相关性分析。与此同时，根据变异在蛋白质水平上的预期影响（低组和高组），将所有 RP 患者分为另外两组：共招募了 29 名患者，其中 11 名是 CNGA1 相关 RP 患者，18 名是 CNGB1 相关 RP 患者。在 CNGA1 和 CNGB1 中分别发现了 5 个和 5 个新变异。CNGA1组和CNGB1组之间以及低视力组和高视力组之间的BCVA相当。与 CNGB1 组相比，CNGA1 组的平均 EZ 宽度更大，尽管没有统计学意义，而低 EZ 宽度组与高 EZ 宽度组之间没有差异。队列中所有患者的眼底照片都显示出典型的 RP 模式，在 SW-AF 图像中，14/21 例患者观察到高荧光环：棒状 CNG 通道相关 RP 在 CNGA1- 和 CNGB1 相关形式中都被证明是一种缓慢进展的疾病，因此是基因增强疗法的理想候选者。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Ophthalmic Research 医学-眼科学

CiteScore

3.80

自引率

4.80%

发文量

审稿时长

6-12 weeks

期刊介绍： ''Ophthalmic Research'' features original papers and reviews reporting on translational and clinical studies. Authors from throughout the world cover research topics on every field in connection with physical, physiologic, pharmacological, biochemical and molecular biological aspects of ophthalmology. This journal also aims to provide a record of international clinical research for both researchers and clinicians in ophthalmology. Finally, the transfer of information from fundamental research to clinical research and clinical practice is particularly welcome.