Abstract：
UNASSIGNED: To gain an insight into the pathophysiology of RAB28-associated inherited retinal degeneration through detailed phenotyping and long-term longitudinal follow-up.
UNASSIGNED: The patient underwent complete ophthalmic examinations. Visual function was assessed with microperimetry, full-field electroretinography (ffERG), imaging with optical coherence tomography (OCT), short-wave (SW), and near-infrared (NIR) fundus autofluorescence (FAF).
UNASSIGNED: A healthy Haitian woman with homozygous pathogenic variants (c.68C > T; p.Ser23Phe) in RAB28 presented at 16 years of age with a four-year history of blurred vision. Visual acuities were 20/125 in each eye, which remained relatively stable since. At age 27, cone ffERGs were non-detectable and borderline for rod-mediated responses. Kinetic fields were full to a V-4e target, undetectable to a small I-4e stimulus. Microperimetry showed an absolute central scotoma surrounded by a pericentral relative scotoma. SD-OCT showed an undetectable or barely detectable foveal and parafoveal photoreceptor outer nuclear layer (ONL), photoreceptor outer segment (POS), and retinal pigment epithelium (RPE) signals and loss of the SW- and NIR-FAF signals. This atrophic region was separated from a normally laminated retina by a narrow transition zone (TZ) of hyper SW- and NIR-FAF that co-localized with preserved ONL but abnormally thinned POS and RPE. There was minimal centrifugal (<100 μm) expansion over a six-year period.
UNASSIGNED: The cone-rod dystrophy phenotype documented herein supports a critical role of RAB28 for cone function and POS maintenance. Severe central photoreceptor and RPE loss with a predilection for POS loss in TZs suggests possible disruptions of complex mechanisms that maintain central cone photoreceptor and RPE homeostasis.
UNASSIGNED: The patient underwent complete ophthalmic examinations. Visual function was assessed with microperimetry, full-field electroretinography (ffERG), imaging with optical coherence tomography (OCT), short-wave (SW), and near-infrared (NIR) fundus autofluorescence (FAF).
UNASSIGNED: A healthy Haitian woman with homozygous pathogenic variants (c.68C > T; p.Ser23Phe) in RAB28 presented at 16 years of age with a four-year history of blurred vision. Visual acuities were 20/125 in each eye, which remained relatively stable since. At age 27, cone ffERGs were non-detectable and borderline for rod-mediated responses. Kinetic fields were full to a V-4e target, undetectable to a small I-4e stimulus. Microperimetry showed an absolute central scotoma surrounded by a pericentral relative scotoma. SD-OCT showed an undetectable or barely detectable foveal and parafoveal photoreceptor outer nuclear layer (ONL), photoreceptor outer segment (POS), and retinal pigment epithelium (RPE) signals and loss of the SW- and NIR-FAF signals. This atrophic region was separated from a normally laminated retina by a narrow transition zone (TZ) of hyper SW- and NIR-FAF that co-localized with preserved ONL but abnormally thinned POS and RPE. There was minimal centrifugal (<100 μm) expansion over a six-year period.
UNASSIGNED: The cone-rod dystrophy phenotype documented herein supports a critical role of RAB28 for cone function and POS maintenance. Severe central photoreceptor and RPE loss with a predilection for POS loss in TZs suggests possible disruptions of complex mechanisms that maintain central cone photoreceptor and RPE homeostasis.
摘要：
■通过详细的表型分析和长期纵向随访，深入了解RAB28相关遗传性视网膜变性的病理生理学。
■患者接受了完整的眼科检查。用显微视野法评估视觉功能，全场视网膜电图（ffERG），光学相干断层扫描(OCT)成像,短波（SW），和近红外(NIR)眼底自发荧光(FAF)。
■一名健康的海地妇女，在RAB28中具有纯合致病变异（c.68C>T；p.Ser23Phe），在16岁时出现视力模糊的四年病史。每只眼睛的视力为20/125，此后保持相对稳定。在27岁时，视锥ffERG是不可检测的，并且是杆介导的反应的边界。动力场充满了V-4e目标，无法检测到一个小的I-4e刺激。显微视野检查显示绝对中央暗点被中央周围相对暗点包围。SD-OCT显示无法检测到或几乎无法检测到的中央凹和旁凹光感受器外核层（ONL），感光体外段(POS)，和视网膜色素上皮(RPE)信号以及SW-和NIR-FAF信号的丢失。该萎缩性区域通过超SW-和NIR-FAF的狭窄过渡区（TZ）与正常层状视网膜分开，该过渡区与保留的ONL共定位，但POS和RPE异常变薄。在6年期间存在最小的离心(<100μm)膨胀。
■本文记载的锥-杆营养不良表型支持RAB28对锥功能和POS维持的关键作用。严重的中央光感受器和RPE损失以及TZs中POS损失的倾向表明可能破坏维持中央圆锥光感受器和RPE稳态的复杂机制。
■患者接受了完整的眼科检查。用显微视野法评估视觉功能，全场视网膜电图（ffERG），光学相干断层扫描(OCT)成像,短波（SW），和近红外(NIR)眼底自发荧光(FAF)。
■一名健康的海地妇女，在RAB28中具有纯合致病变异（c.68C>T；p.Ser23Phe），在16岁时出现视力模糊的四年病史。每只眼睛的视力为20/125，此后保持相对稳定。在27岁时，视锥ffERG是不可检测的，并且是杆介导的反应的边界。动力场充满了V-4e目标，无法检测到一个小的I-4e刺激。显微视野检查显示绝对中央暗点被中央周围相对暗点包围。SD-OCT显示无法检测到或几乎无法检测到的中央凹和旁凹光感受器外核层（ONL），感光体外段(POS)，和视网膜色素上皮(RPE)信号以及SW-和NIR-FAF信号的丢失。该萎缩性区域通过超SW-和NIR-FAF的狭窄过渡区（TZ）与正常层状视网膜分开，该过渡区与保留的ONL共定位，但POS和RPE异常变薄。在6年期间存在最小的离心(<100μm)膨胀。
■本文记载的锥-杆营养不良表型支持RAB28对锥功能和POS维持的关键作用。严重的中央光感受器和RPE损失以及TZs中POS损失的倾向表明可能破坏维持中央圆锥光感受器和RPE稳态的复杂机制。
