Late development of vitelliform lesions and flecks in a patient with Best disease - Clinicopathologic correlation
Late development of vitelliform lesions and flecks in a patient with Best disease - Clinicopathologic correlation
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DOI：
10.1001/archopht.123.11.1588
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发表时间：
2005-11-01
影响因子：
--
通讯作者：
Stone, EM
中科院分区：
文献类型：
--
作者：
Mullins, RF;Oh, KT;Stone, EM
目的：提供出现Best疾病临床特征的患者的临床病理学结果（通常被认为是青少年黄斑变性）在75岁时被记录为在51岁时眼底镜检查正常。设计：Best病大家族成员，VMD2基因中存在Y227N突变（负责该疾病的基因，其编码雌激素蛋白），在75岁时在双眼中出现小的卵黄状病变，随后在视网膜色素上皮（RPE）水平上出现黄色斑点状沉积物，这也在家族成员的眼底照片中被鉴定。结果：视网膜外核层明显变薄，黄斑部变薄尤为明显。这种衰减通常与正常RPE相关。在中央黄斑中存在大面积的光感受器变性，伴随下面的RPE细胞的损失。在该区域之外，RPE密度在正常范围内。周围皱褶是基底层沉积物和玻璃疣的簇。Bestrophin免疫组化显示标记沿着基底侧和顶膜的RPE.Conclusions：最好的疾病的特点的调查结果可能不会表现在一个分子受影响的个人，直到晚年的生活。在某些家族中，斑萎蛋白的突变似乎导致黄斑外的细胞外存款形成。RPE中的bestrophin分布表明，该蛋白质可能在具有Y227N突变的Best疾病患者中被错误定位，并且这可能是相关RPE和感光细胞功能障碍的原因。
Objective: To provide the clinicopathologic findings of a patient who developed the clinical characteristics of Best disease (typically considered a juvenile macular degeneration) at the age of 75 years after being documented to be ophthalmoscopically normal at the age of 51 years.Design: A member of a large family with Best disease, possessing a Y227N mutation in the VMD2 gene (the gene responsible for the disease, which encodes the bestrophin protein), developed small vitelliform lesions in both eyes at the age of 75 years and later developed yellow flecklike depositions at the level of the retinal pigment epithelium (RPE), which were also identified in fundus photographs of family members. The patient died at the age of 91 years, and the histological features of the macular lesion and peripheral flecks were examined.Results: Histopathologically, the retinal outer nuclear layer was attenuated, particularly in the macula. This attenuation was frequently associated with normal RPE. A large area of photoreceptor degeneration was present in the central macula, with loss of the underlying RPE cells. Outside of this region, the RPE density was within normal limits. The peripheral flecks were clusters of basal laminar deposits and drusen. Bestrophin immunohistochemistry revealed labeling along both the basolateral and apical membranes of the RPE.Conclusions: Findings characteristic of Best disease may not manifest in a molecularly affected individual until late in life. Mutations in bestrophin appear to lead to extracellular deposit formation outside the macula in some families. The distribution of bestrophin in the RPE suggests that the protein may be mistargeted in those with Best disease who have the Y227N mutation, and that this may be a cause of the associated RPE and photoreceptor dysfunction.