Longitudinal Analysis of a Resolving Foveomacular Vitelliform Lesion in ABCA4 Disease.
Longitudinal Analysis of a Resolving Foveomacular Vitelliform Lesion in ABCA4 Disease.
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DOI：
10.1016/j.oret.2022.04.005
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发表时间：
2022-09
影响因子：
4.5
通讯作者：
Allikmets, Rando
中科院分区：
文献类型：
--
作者：
Lee, Winston;Su, Pei -Yin;Zernant, Jana;Nagasaki, Takayuki;Tsang, Stephen H.;Allikmets, Rando
描述ABCA 4疾病背景下双侧黄斑中心凹卵黄状病变的纵向进展和表型相关性。病例报告和横断面队列研究19例确诊为ABCA 4疾病的患者，表现出光学间隙表型。多次访视时的多模式视网膜成像包括自体荧光成像、光谱域光学相干断层扫描（SD-OCT）和OCT血管造影。分析眼电图（EOG）和全视野视网膜电图（ffERG）检测结果。进行外显子组测序用于诊断确认和其他变异的验证。光峰：EOG上的暗槽比（Arden比）; SD-OCT上各种视网膜层的厚度和正面图; 488 nm和787 nm自体荧光图像上的面积测量;来自外显子组测序的卵黄状相关基因中存在变异。一位25岁的白人男性，因卵黄状液体组成的中央凹病变而出现双侧中心视力丧失。EOG检测与脑啡肽病（Arden比率= 1.62）不一致，ffERG未检测到普遍的视杆细胞或视锥细胞功能障碍。外显子组测序鉴定了致病性变体，c.5882G>A（p.（Gly1961Glu））和c.4139C>T（p.（Pro 1380 Leu）），而没有其他卵黄相关基因。在病变邻近区域发现光感受器相关层的显着变薄和异常反射率以及近红外自发荧光异常。30个月后卵黄状液体完全吸收，之后光学间隙病变表现出扩大和“肿胀”的外观。对来自大型ABCA 4疾病数据库（n=602）的额外病例进行表型筛选，确定了18名处于不同光学间隙病变形成阶段的额外患者，其中大多数人携带c.5882G>A（p.（Gly 1961 Glu））变异（P<0.001）。至少有5/18例（31.6%）患者表现出明显的“肿胀”外观的光学间隙病变，而其他患者的病变在检查过程中保持不变。黄斑凹卵黄样沉积是ABCA 4疾病的一种机制一致但罕见的表现。具体地说，这种疾病表型可能与c.5882G>A（p.（Gly 1961 Glu））等位基因和光学间隙病变。双侧黄斑中心凹卵黄样病变是罕见的表现光学间隙病变与p。在ABCA 4疾病患者中，Gly 1961 Glu变异体具有与其他已知卵黄样相关疾病可区分的潜在临床特征。
To describe the longitudinal progression and phenotypic association of bilateral foveomacular vitelliform lesions in the setting of ABCA4 disease Case report and cross-sectional cohort study 19 patients with confirmed ABCA4 disease exhibiting the optical gap phenotype Multi-modal retinal imaging across multiple visits included autofluorescence imaging, spectral domain-optical coherence tomography (SD-OCT) and OCT angiography. Electrooculogram (EOG) and full-field electroretinogram (ffERG) testing results were analyzed. Exome sequencing was performed for diagnostic confirmation and verification of other variation. Light peak: dark trough ratio (Arden ratio) on EOG; thickness and en face maps of various retinal layers on SD-OCT; area measurements on 488-nm and 787-nm autofluorescence images; presence of variation in vitelliform-associated genes from exome sequencing. A 25-year-old Caucasian man presented with bilateral central vision loss due to foveal lesions consisting of vitelliform fluid. EOG testing was inconsistent with bestrophinopathy (Arden ratio = 1.62), and no generalized rod or cone dysfunction was detected on ffERG. Exome sequencing identified pathogenic variants, c.5882G>A (p.(Gly1961Glu)) and c.4139C>T (p.(Pro1380Leu)) in ABCA4 and no other vitelliform-associated genes. Significant thinning and abnormal reflectivity of photoreceptor-attributable layers and near infrared autofluorescence abnormalities were found in lesion-adjacent areas. Complete resorption of vitelliform fluid occurred after 30 months, after which the optical gap lesions exhibited an enlarged and “swollen” appearance. Phenotypic screening for additional cases from a large ABCA4 disease database (n=602) identified 18 additional patients at various stages of optical gap lesion formation, most of whom harbored the c.5882G>A (p.(Gly1961Glu)) variant (P<0.001), although none had apparent vitelliform fluid. At least 5/18 (31.6%) patients exhibited optical gaps lesions with the distinct “swollen” appearance while lesions remained unperturbed in other patients over the course of examination. Foveomacular vitelliform deposition is a mechanistically congruent but rare manifestation of ABCA4 disease. Specifically, this disease phenotype may be clinically associated with the c.5882G>A (p.(Gly1961Glu)) allele and optical gap lesions. Bilateral foveomacular vitelliform lesions are rare manifestations of optical gap lesions associated with the p.(Gly1961Glu) variant in ABCA4 disease patients who have underlying clinical features that distinguishable from other known vitelliform-associated disorders.
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影响因子：
4.4
作者：
Greenstein VC;Nunez J;Lee W;Schuerch K;Fortune B;Tsang SH;Allikmets R;Sparrow JR;Hood DC
通讯作者：
Hood DC
影响因子：
9.8
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通讯作者：
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影响因子：
4.4
作者：
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通讯作者：
Delori, Francois C.
影响因子：
4.4
作者：
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通讯作者：
Sparrow, Janet R.
影响因子：
3.9
作者：
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通讯作者：
Sarks, SH