背景:隐匿性黄斑营养不良(OMD),主要由色素性视网膜炎1样1(RP1L1)变体引起,是一种复杂的视网膜疾病,其特征是进行性视力丧失和正常的眼底外观。本研究旨在探讨OMD在中国患者中的不同表型表达和基因型相关性。包括一例罕见的与RP1L1相关的卵形黄斑营养不良(VMD)。
方法:我们分析了7名OMD患者和1名VMD患者,所有具有杂合致病性RP1L1变体。临床评估包括最佳矫正视力(BCVA),视野测试,谱域光学相干断层扫描(SD-OCT)多焦视网膜电图(mfERGs),和显微视野。下一代测序用于遗传分析。
结果:OMD患者表现出一系列的表型变异性。大多数(7个中的5个)具有RP1L1变体c.133C>T;p.R45W,与中心视力丧失和SD-OCT和mfERG的特定模式相关。两名患者表现出不同的RP1L1变体(c.3599G>T;p.G1200V和c.2880G>C;p.W960C),呈现温和的表型。SD-OCT显示光感受器层变化,大多数患者在中央环中显示mfERG反应降低。有趣的是,观察到与RP1L1变体相关的VMD的独特病例,与传统的OMD演示不同。
结论:这项研究强调了OMD内的表型多样性和更广泛的RP1L1相关黄斑营养不良,包括与VMD的新颖联系。研究结果强调了RP1L1变异在确定临床表现时的复杂性。强调需要对黄斑营养不良进行全面的遗传和临床评估。
BACKGROUND: Occult Macular Dystrophy (OMD), primarily caused by retinitis pigmentosa 1-like 1 (RP1L1) variants, is a complex retinal disease characterised by progressive vision loss and a normal fundus appearance. This study aims to investigate the diverse phenotypic expressions and genotypic correlations of OMD in Chinese patients, including a rare case of Vitelliform Macular Dystrophy (VMD) associated with RP1L1.
METHODS: We analysed seven OMD patients and one VMD patient, all with heterozygous pathogenic RP1L1 variants. Clinical assessments included Best Corrected Visual Acuity (BCVA), visual field testing, Spectral Domain Optical Coherence Tomography (SD-OCT), multifocal Electroretinograms (mfERGs), and microperimetry. Next-generation sequencing was utilised for genetic analysis.
RESULTS: The OMD patients displayed a range of phenotypic variability. Most (5 out of 7) had the RP1L1 variant c.133 C > T; p.R45W, associated with central vision loss and specific patterns in SD-OCT and mfERG. Two patients exhibited different RP1L1 variants (c.3599G > T; p.G1200V and c.2880G > C; p.W960C), presenting milder phenotypes. SD-OCT revealed photoreceptor layer changes, with most patients showing decreased mfERG responses in the central rings. Interestingly, a unique case of VMD linked to the RP1L1 variant was observed, distinct from traditional OMD presentations.
CONCLUSIONS: This study highlights the phenotypic diversity within OMD and the broader spectrum of RP1L1-associated macular dystrophies, including a novel association with VMD. The findings emphasise the complexity of RP1L1 variants in determining clinical manifestations, underscoring the need for comprehensive genetic and clinical evaluations in macular dystrophies.