Scheie Eye Institute at the Perelman Center for Advanced Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Center for Advanced Retinal and Ocular Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Ophthalmic Genet. 2021 Jun;42(3):252-265. doi: 10.1080/13816810.2021.1888132. Epub 2021 Mar 17.
: To provide a detailed ophthalmic phenotype of two male patients with Bardet-Biedl Syndrome (BBS) due to mutations in the gene: Two brothers ages 26 (Patient 1, P1) and 23 (P2) underwent comprehensive ophthalmic evaluations over three years. Visual function was assessed with full-field electroretinograms (ffERGs), kinetic and chromatic perimetry, multimodal imaging with spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF) with short- (SW) and near-infrared (NIR) excitation lights and adaptive optics scanning light ophthalmoscopy (AOSLO).: Both siblings had a history of obesity and postaxial polydactyly; P2 had diagnoses of type 1 Diabetes Mellitus, Addison's disease, high-functioning autism-spectrum disorder and -12D myopia. Visual acuities were better than 20/30. Kinetic fields were moderately constricted. Cone-mediated ffERGs were undetectable, rod ERGs were ~80% of normal mean. Static perimetry showed severe central cone and rod dysfunction. Foveal to parafoveal hypoautofluorescence, most obvious on NIR-FAF, co-localized with outer segment shortening/loss and outer nuclear layer thinning by SD-OCT, and with reduced photoreceptors densities by AOSLO. A structural-functional dissociation was confirmed for cone- and rod-mediated parameters. Worsening of the above abnormalities was documented by SD-OCT and FAF in P2 at 3 years. Gene screening identified compound heterozygous mutations in (p.Val266Glu: c.797 T > A of maternal origin; c.1781_1783delCAT, paternal) in both patients.: -associated retinal degeneration may present as a progressive cone-rod dystrophy pattern, reminiscent of both the murine and non-human primate models of the disease. Predominantly central retinal abnormalities in both cone and rod photoreceptors showed a structural-functional dissociation, an ideal scenario for gene augmentation treatments.
为了提供两名由于基因突变导致 Bardet-Biedl 综合征（BBS）的男性患者的详细眼科表型：两名年龄分别为 26 岁（患者 1，P1）和 23 岁（P2）的兄弟在三年内接受了全面的眼科评估。使用全视野视网膜电图（ffERG）、动态和色度视野计、光谱域光学相干断层扫描（SD-OCT）的多模态成像、短（SW）和近红外（NIR）激发光的眼底自发荧光（FAF）以及自适应光学扫描激光检眼镜（AOSLO）评估视觉功能。：这对兄弟都有肥胖和轴后多指的病史；P2 还被诊断出患有 1 型糖尿病、艾迪生病、高功能自闭症谱系障碍和 -12D 近视。视力均优于 20/30。动态视野适度受限。锥细胞介导的 ffERG 无法检测到，杆 ERG 约为正常平均值的 80%。静态视野检查显示严重的中心锥细胞和杆细胞功能障碍。黄斑至旁黄斑区自发荧光减弱，以 NIR-FAF 最明显，与 SD-OCT 显示的外节缩短/缺失和外核层变薄以及 AOSLO 显示的光感受器密度降低有关。通过 AOSLO 证实了锥细胞和杆细胞介导的参数之间存在结构-功能分离。P2 在 3 年内通过 SD-OCT 和 FAF 记录到上述异常的恶化。基因筛查在两名患者中均发现了基因（p.Val266Glu：母源性 c.797 T > A；父源性 c.1781_1783delCAT）的复合杂合突变。：-相关的视网膜变性可能表现为进行性的锥-杆细胞营养不良模式，类似于该疾病的小鼠和非人类灵长类动物模型。在中心和周边视网膜中，两种视锥和视杆细胞都表现出结构-功能分离，这是基因增强治疗的理想场景。
