Lin Siying, Arno Gavin, Robson Anthony G, Schiff Elena R, Mohamed Moin D, Michaelides Michel, Webster Andrew R, Mahroo Omar A
National Institute of Health Research Biomedical Research Centre at Moorfields Eye Hospital and The UCL Institute of Ophthalmology, London, UK.
UCL Institute of Ophthalmology, University College London, London, UK.
Eye (Lond). 2025 Apr;39(5):951-957. doi: 10.1038/s41433-024-03522-2. Epub 2024 Dec 4.
Variants in CRX are associated with dominantly inherited retinopathy with considerable phenotypic variability. Many patients have central retinal degeneration; in some patients, we have observed an additional focus of degeneration in the nasal retina. This study explores this phenotypic association amongst patients with CRX-associated disease.
A retrospective review was conducted for all patients with dominant CRX-associated retinopathy at two UK centres. Analysis focused on patients with available ultra-widefield autofluorescence imaging and aimed to identify those with a specific bifocal degeneration pattern involving the nasal retina in both eyes.
Sixty patients were identified, with ultra-widefield fundus imaging available for 50 patients. Of these, six male patients aged 26-74 years displayed a distinct pattern characterised by central retinal degeneration and an additional discrete area of altered autofluorescence in the nasal periphery. Pattern and full-field ERGs indicated macular dysfunction in all 6 cases, with generalised cone (n = 2) or cone and rod (n = 4) system involvement, with a locus that appeared to be post-phototransduction. The CRX variants found in these patients included missense variants (n = 2), frameshifting variants (n = 3), and a CRX whole gene deletion (n = 1), with no clear genotype-phenotype correlation identified.
We report a distinct pattern of bifocal retinal degeneration in some cases of CRX-associated retinopathy (12% in our cohort), not typically seen in other forms of inherited retinal disease. Recognising such phenotypes can guide genetic investigations or their interpretation, facilitating molecular diagnoses for effective family counselling, given the autosomal dominant inheritance and phenotypic variability of CRX-associated retinopathy.
CRX基因变异与具有显著表型变异性的显性遗传性视网膜病变相关。许多患者存在视网膜中央变性；在一些患者中，我们观察到鼻侧视网膜存在额外的变性病灶。本研究探讨了CRX相关疾病患者中的这种表型关联。
对英国两个中心所有患有显性CRX相关视网膜病变的患者进行回顾性研究。分析聚焦于有超广域自发荧光成像资料的患者，旨在识别双眼均存在涉及鼻侧视网膜的特定双灶性变性模式的患者。
共识别出60例患者，其中50例有超广域眼底成像资料。在这些患者中，6例年龄在26 - 74岁的男性患者呈现出一种独特的模式，其特征为视网膜中央变性以及鼻侧周边存在一个额外的自发荧光改变的离散区域。模式和全视野视网膜电图显示所有6例患者均存在黄斑功能障碍，累及广义视锥系统（n = 2）或视锥和视杆系统（n = 4），其病变位点似乎位于光转导之后。这些患者中发现的CRX变异包括错义变异（n = 2）、移码变异（n = 3）和CRX全基因缺失（n = 1），未发现明确的基因型 - 表型相关性。
我们报告了在一些CRX相关视网膜病变病例中存在一种独特的双灶性视网膜变性模式（在我们的队列中占12%），这在其他形式的遗传性视网膜疾病中并不常见。鉴于CRX相关视网膜病变的常染色体显性遗传和表型变异性，识别此类表型可指导基因研究或其解读，有助于进行分子诊断以提供有效的遗传咨询。
