Department of Ophthalmology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Klin Monbl Augenheilkd. 2023 Apr;240(4):536-543. doi: 10.1055/a-2034-6250. Epub 2023 Apr 25.
The aim of the study was to describe the clinical and genetic correlation of a c.469 G>A p.(Asp157Asn) heterozygous pathogenic variant in PRPH2 in two siblings of Italian origin.
Both patients underwent ophthalmic examination, electrophysiological testing, autofluorescence imaging, and optical coherence tomography (OCT). Screening for pathogenic variants of the obtained DNA from the family members was carried out.
The 52-year-old (♀, index patient) and 50-year-old (♂) siblings had BCVA (OD and OS) of 20/20 and 20/16 (♀) and 20/25 and 20/40 (♂), respectively, and suffered increased sensitivity to glare. Yellow irregular macular deposits, numerous small irregular hypo- and hyperreflective spots at the posterior pole, a patchy loss of photoreceptors, and retinal pigment epithelium (RPE) in the perifoveal region were seen. Electrophysiology showed dysfunction of rods and cones, with more affected cone dysfunction in the index patient, contrary to the generalised rod dysfunction in the brother of the index patient. The clinical, electrophysiological, and multimodal imaging findings of both siblings pointed towards Stargardt retinopathy with heterogenic presentation. The DNA analysis identified an autosomal dominant c.469 G>A p.(Asp157Asn) heterozygous pathogenic variant in PRPH2 associated with autosomal dominant cone-rod dystrophy and rod-cone dystrophy. PRPH2 codes for peripherin-2, a membrane protein that consists of 346 amino acids.
Our findings confirm a heterogeneity in clinical presentation associated with pathogenic variants in PRPH2. It may follow either an autosomal dominant or an autosomal recessive mode of inheritance and show a very heterogeneous clinical manifestation of retinal degeneration, e.g., autosomal dominant retinitis pigmentosa (♂ sibling; II-3) and autosomal dominant cone-rod dystrophy (index ♀ sibling; II-2), autosomal dominant macular dystrophy, and also autosomal recessive retinitis pigmentosa.
本研究旨在描述 2 名意大利裔兄弟姐妹中 PRPH2 基因 c.469 G>A p.(Asp157Asn)杂合致病性变异的临床和遗传相关性。
两名患者均接受了眼科检查、电生理测试、自发荧光成像和光学相干断层扫描（OCT）。对家族成员获得的 DNA 进行致病性变异筛查。
52 岁（♀，索引患者）和 50 岁（♂）的兄弟姐妹的最佳矫正视力（OD 和 OS）分别为 20/20 和 20/16（♀）和 20/25 和 20/40（♂），并伴有畏光敏感性增加。黄斑后极部可见不规则黄色斑点状沉积，大量小的不规则低反射和高反射斑点，光感受器和视网膜色素上皮（RPE）在中心凹周围呈斑片状丢失。电生理检查显示视杆和视锥功能障碍，与哥哥的普遍视杆功能障碍相反，索引患者的视锥功能障碍更为严重。两名兄弟姐妹的临床、电生理和多模态成像结果均指向表现型异质性的 Stargardt 视网膜病变。DNA 分析发现 PRPH2 基因的常染色体显性 c.469 G>A p.(Asp157Asn)杂合致病性变异，与常染色体显性视锥-视杆营养不良和视杆-视锥营养不良相关。PRPH2 编码周边蛋白-2，这是一种由 346 个氨基酸组成的膜蛋白。
我们的研究结果证实了 PRPH2 基因致病性变异与临床表型异质性相关。它可能遵循常染色体显性或常染色体隐性遗传模式，表现出非常异质性的视网膜变性临床表现，例如常染色体显性视网膜色素变性（♂ 兄弟；II-3）和常染色体显性视锥-视杆营养不良（指数♀姐妹；II-2）、常染色体显性黄斑营养不良，以及常染色体隐性视网膜色素变性。
