ABSTRACT

Purpose

To describe the clinical, electrophysiological, and molecular features of an unusual macula-predominant retinopathy in two unrelated probands with biallelic variants in RDH12.

Methods

Retrospective case series

Results

A 29-year-old female presented with visual loss since the age of 14 years. Retinal examination revealed symmetric outer retinal atrophy in the posterior pole with peripapillary sparing. Fundus autofluorescence (AF) showed patchy loss of AF in the posterior pole, with hyper-autofluorescent borders. Optical coherence tomography (OCT) showed loss of the macular outer retinal layers. Pattern electroretinography (PERG) showed macular dysfunction and full-field ERG indicated mild loss of photoreceptor function. Next-generation sequencing (NGS) identified two variants in RDH12: p.(Arg234His) and c.448 + 1 G > A in trans. The second patient was a 10-year-old male with bilateral macular changes and visual loss. Retinal examination showed bilateral macular cloverleaf-like outer retinal changes, with relative foveal sparing. Fundus AF showed bilateral macular hypo-autofluorescent patches with a border of increased signal and preserved foveal AF. OCT showed attenuation of the perifoveal outer retinal layers in the regions of reduced AF signal. PERG showed macular dysfunction, but the full-field ERG was normal. NGS and whole-genome sequencing identified two variants in RDH12: p.(Arg234His) and p.(Cys245_Leu247deI) in trans.

Conclusions

Disease-causing variants in RDH12 are typically associated with early-onset severe retinal dystrophy with significant macular involvement. Hypomorphic alleles of this gene cause relatively mild retinopathy with predominant macular involvement. This phenotype demonstrates the vulnerability of the macular photoreceptors to certain perturbations of RDH12.

中文翻译：

---

黄斑为主的视网膜病变，与RDH12中的双等位基因变异有关。

摘要

目的

要描述在RDH12中具有双等位基因变异的两个不相关先证者中异常黄斑为主的视网膜病变的临床，电生理和分子特征。

方法

回顾案系列

结果

一名29岁的女性自14岁起出现视力下降。视网膜检查发现在后极对称的外部视网膜萎缩，并伴有乳头周围的保留。眼底自发荧光（AF）显示后极的AF呈片状丢失，具有超自发荧光边界。光学相干断层扫描（OCT）显示视网膜黄斑外层丢失。模式视网膜电图（PERG）显示黄斑功能不全，全视野ERG显示光感受器功能轻度丧失。下一代测序（NGS）在RDH12中鉴定出两个变体：p。（Arg234His）和c.448 + 1 G> A反式。第二例患者是一名10岁的男性，患有双侧黄斑改变和视力丧失。视网膜检查显示双侧黄斑苜蓿叶状样外部视网膜改变，相对中央凹。眼底房颤显示双侧黄斑部自体荧光斑，信号边界增加，并保留了中央凹房颤。OCT显示在AF信号减弱的区域中，视网膜中央凹周围视网膜层减弱。PERG显示黄斑功能不全，但全视野ERG正常。NGS和全基因组测序确定了RDH12中的两个变异：反式中的p。（Arg234His）和p。（Cys245_Leu247deI）。

结论

RDH12中的致病变异通常与早期发作的严重视网膜营养不良有关，并伴有大量黄斑病变。该基因的亚同型等位基因引起黄斑受累的相对轻度的视网膜病变。这种表型表明黄斑感光细胞对RDH12某些摄动的脆弱性。