Purpose

To describe in detail the phenotype of a patient with compound heterozygous mutations in ZNF408 and an adult-onset pigmentary retinopathy rather than familial exudative vitreoretinopathy as expected with heterozygous mutations in this gene.

Methods

A 70-year-old male presented with a pigmentary retinopathy, which prompted a genetic evaluation that revealed two variants in trans in the ZNF408 gene. He underwent an ophthalmic examination, kinetic fields, electroretinography (ERG), spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence, wide-angle fluorescein angiography and near-infrared imaging.

Results

Visual acuity was 20/20 for both eyes. Fundus examination showed epiretinal membrane, vascular attenuation and peripheral bone spicule pigmentation in both eyes. Fluorescein angiography showed no vascular anomalies in both eyes. Fundus autofluorescence showed a preserved island of fundus autofluorescence centrally. Visual field by kinetic perimetry (V-4e stimulus) showed generalized constriction to 40 degrees of eccentricity and by an I-4e target showed generalized constriction to 10 degrees of eccentricity. ERG showed detectable but reduced cone-mediated responses. SD-OCT demonstrated preserved outer nuclear layer thickness centrally, which decreased with eccentricity. Static perimetry showed substantial rod and cone sensitivities centrally that declined with eccentricity. A next-generation sequencing panel revealed bi-allelic variants (p.Arg567Ter; c.1699C > T and p.Leu566His; c.1697 T > A) in the ZNF408 gene.

Conclusions

ZNF408-associated retinal dystrophies can present with predominantly retinal findings and should be considered in the differential diagnosis of retinitis pigmentosa. Our study revealed a novel variant p.L566H, which to our knowledge has not previously been reported.

中文翻译：

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迟发性色素性视网膜病变和相对保留的中央视网膜患者的 ZNF408 复合杂合突变

目的

详细描述具有ZNF408复合杂合突变和成人发病的色素性视网膜病变的患者的表型，而不是该基因杂合突变所预期的家族性渗出性玻璃体视网膜病变。

方法

一名 70 岁男性出现色素性视网膜病变，这促使一项遗传评估发现ZNF408基因中有两个反式变异。他接受了眼科检查、动力学场、视网膜电图 (ERG)、光谱域光学相干断层扫描 (SD-OCT)、眼底自发荧光、广角荧光素血管造影和近红外成像。

结果

双眼的视力为 20/20。眼底检查显示双眼视网膜前膜、血管衰减和外周骨针状色素沉着。荧光素血管造影显示双眼无血管异常。眼底自发荧光显示中央有一个保留的眼底自发荧光岛。动态视野测量（V-4e 刺激）的视野显示到 40 度离心率的广义收缩，I-4e 目标显示到 10 度离心率的广义收缩。ERG 显示可检测但减少的视锥介导的反应。SD-OCT 显示中央保留的外核层厚度，随着离心率的降低而减小。静态视野测量显示大量的杆和锥体敏感性集中，随着离心率的下降而下降。下一代测序面板揭示了双等位基因变异 (p. Arg567Ter; c.1699C > T 和 p.Leu566His；c.1697 T > A) 在ZNF408基因。

结论

ZNF408相关的视网膜营养不良可表现为主要的视网膜表现，应在视网膜色素变性的鉴别诊断中予以考虑。我们的研究揭示了一种新的变体 p.L566H，据我们所知，以前没有报道过。