The Natural History of Inherited Retinal Dystrophy Due to Biallelic Mutations in the RPE65 Gene
The Natural History of Inherited Retinal Dystrophy Due to Biallelic Mutations in the RPE65 Gene
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DOI：
10.1016/j.ajo.2018.09.024
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发表时间：
2019-03-01
影响因子：
4.2
通讯作者：
Reape, Kathleen Z.
中科院分区：
文献类型：
--
作者：
Chung, Daniel C.;Bertelsen, Mette;Reape, Kathleen Z.
目得：描述双等位基因RPE 65突变相关的遗传性视网膜营养不良（IRD）个体随时间变化的视觉参数的自然史;描述致病突变的范围;确定潜在的基因型/表型关系;并描述各种临床diagnosis.Design：Global，multicenter，retrospective chart review.METHODS：Study Population：Seventy individuals with biallelic RPE 65 mutation-associated IRD。程序：从患者病历中提取数据。测量值：视力（VA）、Goldmann视野（GVF）、光学相干断层扫描、色觉测试、光敏感度测试和视网膜电图（视网膜成像和眼底照相在可用时收集并分析）。结果：VA随着年龄的增长呈非线性正加速关系（P < .001）。GVF随年龄增长而下降（V4 e和III 4 e均P <0.0001），与V4 e相比，III 4 e刺激的GVF下降更快（左眼P = 0.0114;右眼P = 0.0076）。平均而言，年龄增加1岁，每只眼睛的III 4 e GVF减少了25个总度数，而V4 e GVF减少了37个总度数，尽管观察到个体差异。共有78个临床诊断和56个独特的RPE 65突变记录，没有明显的RPE 65突变基因型/表型relationships.CONCLUSIONS：临床诊断和缺乏一致的RPE 65突变表型相关性的数量强调需要进行基因检测。年龄与VA和GVF恶化之间的显著关系突出了功能性视网膜随时间的进行性丧失。这些数据可能对双等位基因RPE 65突变所致IRD的最佳治疗时机产生影响。(C)2018爱思唯尔公司All rights reserved.
PURPOSE: To delineate the natural history of visual parameters over time in individuals with biallelic RPE65 mutation-associated inherited retinal dystrophy (IRD); describe the range of causative mutations; determine potential genotype/phenotype relationships; and describe the variety of clinical diagnoses.DESIGN: Global, multicenter, retrospective chart review.METHODS: STUDY POPULATION: Seventy individuals with biallelic RPE65 mutation-associated IRD. PROCEDURES: Data were extracted from patient charts. MEASUREMENTS: Visual acuity (VA), Goldmann visual field (GVF), optical coherence tomography, color vision testing, light sensitivity testing, and electroretinograms (retinal imaging and fundus photography were collected and analyzed when available).RESULTS: VA decreased with age in a nonlinear, positive-acceleration relationship (P < .001). GVF decreased with age (P < .0001 for both V4e and III4e), with faster GVF decrease for III4e stimulus vs V4e (P = .0114, left eye; P = .0076, right eye). On average, a 1-year increase in age decreased III4e GVF by similar to 25 sum total degrees in each eye while V4e GVF decreased by similar to 37 sum total degrees in each eye, although individual variability was observed. A total of 78 clinical diagnoses and 56 unique RPE65 mutations were recorded, without discernible RPE65 mutation genotype/phenotype relationships.CONCLUSIONS: The number of clinical diagnoses and lack of a consistent RPE65 mutation-to-phenotype correlation underscore the need for genetic testing. Significant relationships between age and worsening VA and GVF highlight the progressive loss of functional retina over time. These data may have implications for optimal timing of treatment for IRD attributable to biallelic RPE65 mutations. (C) 2018 Elsevier Inc. All rights reserved.