Banjak Malak, Noureldine Jinane, Mousawi Zahraa, Nehme Joseph, Jaffal Lama, El Shamieh Said
Rammal Hassan Rammal Research Laboratory, PhyToxE Research Group, Faculty of Sciences, Lebanese University, Nabatyeh, Lebanon.
Molecular Testing Laboratory, Department of Medical Laboratory Technology, Beirut Arab University, Beirut, Lebanon.
BMJ Open Ophthalmol. 2025 Mar 25;10(1):e002030. doi: 10.1136/bmjophth-2024-002030.
-associated retinal dystrophies (-RDs) exhibit significant genotype-phenotype heterogeneity. This study aimed to elucidate the genotype-phenotype associations of through a systematic analysis of the reported cases.
84 studies, including 373 worldwide participants, were reviewed. These studies were checked for quality using Murad's tool for methodological quality and synthesis of case series and case reports. Clinical data, fundus imaging characteristics and genetic pathogenic variants were analysed.
The quality analysis revealed an overall good quality of the dataset, with some exceptions that do not detract from this trend. A predominance of cone-rod dystrophy (CRD) and Leber congenital amaurosis (LCA) among -RDs (43% and 27%, respectively) was noted. Missense pathogenic variants were significantly associated with macular pigmentation, an absence of peripheral atrophy, an absence of peripheral pigmentation and CRD (p<0.05). In contrast, the indels (98% frameshifts) were associated with pale optic discs, attenuated optic vessels, and peripheral bone spicules, and more severe phenotypes, such as LCA (p<0.05). Pathogenic variants in the homeodomain were associated with cone and/or CRD; others in the OTX tail were linked to LCA.
pathogenic variants are associated with specific phenotypic features.
[疾病名称]相关视网膜营养不良（[疾病名称]-RDs）表现出显著的基因型-表型异质性。本研究旨在通过对已报道病例的系统分析，阐明[疾病名称]的基因型-表型关联。
对84项研究进行了综述，包括全球373名参与者。使用穆拉德的病例系列和病例报告方法学质量及综合评估工具对这些研究进行质量检查。分析了临床数据、眼底成像特征和基因致病变异。
质量分析显示数据集总体质量良好，虽有一些例外情况，但不影响这一趋势。在[疾病名称]-RDs中，以锥杆营养不良（CRD）和莱伯先天性黑蒙（LCA）为主（分别占43%和27%）。错义致病变异与黄斑色素沉着、无周边萎缩、无周边色素沉着及CRD显著相关（p<0.05）。相比之下，插入缺失（98%为移码突变）与视盘苍白、视神经血管变细和周边骨针样改变以及更严重的表型如LCA相关（p<0.05）。同源结构域中的致病变异与视锥和/或CRD相关；OTX尾部的其他变异与LCA相关。
[疾病名称]致病变异与特定的表型特征相关。
