Papadopoulou Laiou C, Preising M N, Bolz H J, Lorenz B
Klinik und Poliklinik für Augenheilkunde, Justus-Liebig-Universität Gießen, Universitätsklinikum Gießen und Marburg GmbH.
Institut für Humangenetik, Universitätsklinikum Köln.
Klin Monbl Augenheilkd. 2017 Mar;234(3):289-302. doi: 10.1055/s-0043-103961. Epub 2017 Mar 29.
Mutations in the gene were identified in patients with early-onset severe retinal dystrophy (EOSRD), childhood-onset and juvenile-onset rod-cone dystrophy. This study describes the phenotypic spectrum of disease-causing -mutations in the first two decades of life. Eight patients, aged three months to 20 years, underwent a full comprehensive ophthalmological examination including best corrected visual acuity testing (BCVA), color vision testing, funduscopy, spectral-domain optical coherence tomography (SD-OCT), and fundus autofluorescence (FAF) recording. Automated and manual retinal layer segmentation of SD-OCT recordings was performed using DIOCTA software. A full-field electroretinography (ffERG, ISCEV Standard) and visual fields were performed in cooperative patients. Five patients carried mutations causing a loss of the corresponding gene product (splice-mutation, nonsense-mutation, frame-shifting mutation). These patients presented with generally reduced vision in the first months of life that never exceeded 0.04 during the observational period. The sixth patient carried a homozygous missense mutation and reached maximal BCVA 0.05 at the age of 6 years. Two further patients, carrying at least one hypomorphic missense-mutation, presented with better preserved visual function with up to 0.5 at the age of 20 years. The recorded ffERG was below threshold in the majority of patients. Visual fields were severely restricted. The photoreceptor layers were significantly reduced in SD-OCT whenever stratification of retinal layers was possible. The inner nuclear layer thickness increased with progressing retinal degeneration. A-Scan analysis revealed better preservation of the retinal stratification in patients with missense mutations. Patients with -mutations presented with a severe phenotype with severely reduced visual acuity from birth. Missense mutations with predicted residual function of the gene product were associated with moderate expression of the disease. Severe and progressive restriction of visual fields occurred in the first decade of life. The reduced retinal stratification indicates a general loss of structural integrity of the retinal layers.
在早发性严重视网膜营养不良（EOSRD）、儿童期和青少年期视锥视杆营养不良患者中发现了该基因的突变。本研究描述了在生命的前二十年中致病突变的疾病表型谱。八名年龄在三个月至20岁之间的患者接受了全面的眼科检查，包括最佳矫正视力测试（BCVA）、色觉测试、眼底检查、光谱域光学相干断层扫描（SD-OCT）和眼底自发荧光（FAF）记录。使用DIOCTA软件对SD-OCT记录进行自动和手动视网膜层分割。对合作的患者进行了全视野视网膜电图（ffERG，ISCEV标准）和视野检查。五名患者携带导致相应基因产物缺失的突变（剪接突变、无义突变、移码突变）。这些患者在生命的最初几个月视力普遍下降，在观察期内从未超过0.04。第六名患者携带纯合错义突变，6岁时达到最大BCVA 0.05。另外两名患者携带至少一个低表达错义突变，在20岁时视力功能保存较好，可达0.5。大多数患者记录的ffERG低于阈值。视野严重受限。只要有可能对视网膜层进行分层，SD-OCT中的光感受器层就会显著减少。随着视网膜变性的进展，内核层厚度增加。A超分析显示错义突变患者的视网膜分层保存较好。携带突变的患者表现出严重的表型，自出生起视力严重下降。预测基因产物具有残余功能的错义突变与疾病的中度表达相关。在生命的第一个十年中出现严重且进行性的视野受限。视网膜分层减少表明视网膜层的结构完整性普遍丧失。
