Unraveling RP1-Associated Retinal Dystrophies: Comprehensive Genetic, Clinical, and Disease Progression Analysis in China.

IF 2.7 3区医学 Q2 OPHTHALMOLOGY

Translational Vision Science & Technology Pub Date : 2026-10-05 DOI:10.1167/tvst.15.10.3

Hong-Li Liu, Ting Li, Ping Xu, Sheng-Hai Zhang, Ji-Hong Wu

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引用次数: 0

Abstract

Purpose: To characterize the clinical manifestations, genetic landscape, and natural history of RP1-associated retinopathy in a Chinese cohort.

Methods: This longitudinal cohort study enrolled and followed 49 patients with genetically confirmed RP1-associated retinopathy. Phenotyping included visual acuity (VA), visual field, full-field stimulus testing (FST), microperimetry, and multimodal imaging. Genetic analysis and variant interpretation followed American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines.

Results: The cohort predominantly presented with retinitis pigmentosa (RP, 91.8%) and bilateral involvement, with overall no significant interocular differences in major functional parameters (all P > 0.05). Median symptom onset age was 20 years (interquartile range, 7.25-33.75). On linear regression analysis, earlier onset age (P = 0.024) and longer disease duration (P = 0.019) correlated with worse VA. Kaplan-Meier analysis estimated that the median age at which patients reached blindness (>1.3 logarithm of the minimum angle of resolution [logMAR]) was 74 years. Quantified decline rates included VA (0.015 logMAR/year) and visual field index (-7.8%/year) in the first decade and FST (0.167 log cd·s/m2/year) and retinal sensitivity (-1.22 dB/year) over two decades. Classic bone-spicule pigmentation was absent in 33.3% of patients. Genetic analysis identified 46 variants; truncating mutations (71.7%) clustered in exon 4, with c.5797C>T as a founder variant (16.3% of alleles). Variants within the upstream one-third of exon 4 were associated with later onset (P = 0.049).

Conclusions: RP1-associated retinopathy manifests as bilateral, atypical RP with quantifiable, duration-dependent decline and a genotype-phenotype correlation linking upstream exon 4 variants to later onset.

Translational relevance: Quantified progression rates and genotype-phenotype correlations inform clinical trial endpoints and patient counseling.

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揭示rp1相关的视网膜营养不良：中国的综合遗传、临床和疾病进展分析。

目的：研究中国人群中rp1相关视网膜病变的临床表现、遗传景观和自然病史。方法：这项纵向队列研究招募并随访了49例遗传证实的rp1相关视网膜病变患者。表型包括视力（VA）、视野、全视野刺激测试（FST）、显微镜观察和多模态成像。遗传分析和变异解释遵循美国医学遗传学和基因组学学院和分子病理学协会的指导方针。结果：该队列以色素性视网膜炎（RP, 91.8%）和双侧受累为主，主要功能参数总体上眼间无显著差异（P < 0.05）。中位发病年龄为20岁（四分位数差为7.25 ~ 33.75）。在线性回归分析中，发病年龄越早（P = 0.024）和病程越长（P = 0.019）与VA越差相关。Kaplan-Meier分析估计，患者失明的中位年龄（>最小分辨角[logMAR]的1.3对数）为74岁。量化的下降率包括前10年的VA （0.015 logMAR/年）和视野指数（-7.8%/年），以及20年的FST （0.167 log cd·s/m2/年）和视网膜灵敏度（-1.22 dB/年）。33.3%的患者没有典型的骨针状色素沉着。遗传分析鉴定出46个变异；截断突变（71.7%）聚集在外显子4，其中c.5797C >t为始发变异（16.3%）。外显子4上游三分之一的变异与晚发病相关（P = 0.049）。结论：rp1相关视网膜病变表现为双侧，非典型RP，具有可量化的，持续时间依赖性的衰退，并且将上游外显子4变异与晚发病联系起来的基因型-表型相关。转化相关性：量化的进展率和基因型-表型相关性为临床试验终点和患者咨询提供信息。

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

Translational Vision Science & Technology Engineering-Biomedical Engineering

CiteScore

5.70

自引率

3.30%

发文量

346

审稿时长

25 weeks

期刊介绍： Translational Vision Science & Technology (TVST), an official journal of the Association for Research in Vision and Ophthalmology (ARVO), an international organization whose purpose is to advance research worldwide into understanding the visual system and preventing, treating and curing its disorders, is an online, open access, peer-reviewed journal emphasizing multidisciplinary research that bridges the gap between basic research and clinical care. A highly qualified and diverse group of Associate Editors and Editorial Board Members is led by Editor-in-Chief Marco Zarbin, MD, PhD, FARVO. The journal covers a broad spectrum of work, including but not limited to: Applications of stem cell technology for regenerative medicine, Development of new animal models of human diseases, Tissue bioengineering, Chemical engineering to improve virus-based gene delivery, Nanotechnology for drug delivery, Design and synthesis of artificial extracellular matrices, Development of a true microsurgical operating environment, Refining data analysis algorithms to improve in vivo imaging technology, Results of Phase 1 clinical trials, Reverse translational ("bedside to bench") research. TVST seeks manuscripts from scientists and clinicians with diverse backgrounds ranging from basic chemistry to ophthalmic surgery that will advance or change the way we understand and/or treat vision-threatening diseases. TVST encourages the use of color, multimedia, hyperlinks, program code and other digital enhancements.