Al-Khuzaei Saoud, Shah Mital, Reginald Arun, Baba Edna, Shanks Morag, Clouston Penny, MacLaren Robert E, Halford Stephanie, De Silva Samantha R, Downes Susan M
Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 9DU, UK.
Genes (Basel). 2025 Aug 27;16(9):1016. doi: 10.3390/genes16091016.
To investigate genotype-phenotype correlations in -retinopathies in a cohort of 36 patients from the Oxford Eye Hospital and report on novel pathogenic variants.
Clinical data, including best corrected visual acuities (BCVA), fundus autofluorescence (FAF), and optical coherence tomography (OCT) imaging, were analysed. Genetic testing was performed using next-generation sequencing (NGS).
In this cohort, 26 different variants, including 8 novel variants, were identified. Variants were clustered in the D2 loop of the protein. A diverse range of phenotypes were observed: pseudo-Stargardt pattern dystrophy (PSPD) (47.2%), adult-onset vitelliform macular dystrophy (AVMD) (22.2%), pattern dystrophy (PD) (25.0%), atypical macular dystrophy (2.8%), and retinitis pigmentosa (RP) (2.8%). The mean age of symptom onset was 44.0 ± 14.4 years. Mean BCVA was 0.20 ± 0.54 logMAR OD and 0.14 ± 0.29 logMAR OS at baseline and 0.33 ± 0.40 logMAR OD and 0.32 ± 0.40 logMAR OS after a mean follow up duration of 6.0 ± 3.2 years (range 1-11 years). A thickened ellipsoid zone (EZ) was noted in 34/36 patients with a mean EZ thickness of 44.3 ± 11.3 µm OD and 42.7 ± 11.6 µm OS. No clear genotype-phenotype correlations were observed.
The significant phenotypic range described in this study is consistent with the previously reported phenotypic variability in retinopathy and emphasises the complexity of establishing genotype-phenotype correlations in this disease. The thickness of the EZ on OCT may serve as a useful biomarker in distinguishing retinopathy from other phenocopies. These findings contribute to improved understanding of retinopathy and help inform diagnosis and genetic counselling.
在牛津眼科医院的36例患者队列中研究视网膜病变的基因型-表型相关性，并报告新的致病变异。
分析临床数据，包括最佳矫正视力（BCVA）、眼底自发荧光（FAF）和光学相干断层扫描（OCT）成像。使用下一代测序（NGS）进行基因检测。
在该队列中，鉴定出26种不同的变异，包括8种新变异。变异聚集在蛋白质的D2环中。观察到多种表型：假性Stargardt样营养不良（PSPD）（47.2%）、成人型卵黄样黄斑营养不良（AVMD）（22.2%）、图案样营养不良（PD）（25.0%）、非典型黄斑营养不良（2.8%）和视网膜色素变性（RP）（2.8%）。症状发作的平均年龄为44.0±14.4岁。基线时平均BCVA右眼为0. \alpha±0.54 logMAR，左眼为0.14±0.29 logMAR，平均随访6.0±3.2年（范围1 - 11年）后，右眼为0.33±0.40 logMAR，左眼为0.32±0.40 logMAR。36例患者中有34例观察到椭圆体带（EZ）增厚，右眼平均EZ厚度为44.3±11.3 µm，左眼为42.7±11.6 µm。未观察到明确的基因型-表型相关性。
本研究中描述的显著表型范围与先前报道的视网膜病变表型变异性一致，并强调了在该疾病中建立基因型-表型相关性的复杂性。OCT上EZ的厚度可能作为区分视网膜病变与其他表型相似疾病的有用生物标志物。这些发现有助于提高对视网膜病变的理解，并有助于指导诊断和遗传咨询。
