Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
Clin Genet. 2018 Dec;94(6):569-574. doi: 10.1111/cge.13447. Epub 2018 Oct 15.
It can be clinically challenging to distinguish dry age-related macular degeneration (AMD) from AMD-mimicking dystrophies, and sometimes misdiagnosis occurs. With upcoming therapies for dry AMD it is important to exclude patients with a different retinal disease from clinical trials. In this study we evaluated the occurrence of AMD-mimicking dystrophies in an AMD cohort. Whole-exome sequencing (WES) was performed in 218 patients with intermediate AMD or geographic atrophy secondary to AMD and 133 control individuals. WES data was analyzed for rare variants in 19 genes associated with autosomal dominant and recessive macular dystrophies mimicking AMD. In three (1.4%) of 218 cases we identified a pathogenic heterozygous variant (PRPH2 c.424C > T; p.R142W) causal for autosomal dominant central areolar choroidal dystrophy (CACD). Phenotypically, these patients all presented with geographic atrophy. In 12 (5.5%) of 218 cases we identified a heterozygous variant of unknown clinical significance, but predicted to be highly deleterious, in genes previously associated with autosomal dominant macular dystrophies. The distinction between AMD and AMD-mimicking dystrophies, such as CACD, can be challenging based on fundus examination alone. Genetic screening for genes associated with macular dystrophies, especially PRPH2, can be beneficial to help identify AMD-mimicking dystrophies.
在临床上，区分干性年龄相关性黄斑变性 (AMD) 与类似 AMD 的营养不良症可能具有挑战性，有时会出现误诊。随着针对干性 AMD 的治疗方法的出现，从临床试验中排除患有不同视网膜疾病的患者非常重要。在这项研究中，我们评估了 AMD 队列中类似 AMD 的营养不良症的发生情况。对 218 名患有中间型 AMD 或 AMD 引起的地图状萎缩以及 133 名对照个体进行了全外显子组测序 (WES)。对与常染色体显性和隐性类似 AMD 的黄斑营养不良症相关的 19 个基因中的罕见变异进行了 WES 数据分析。在 218 例病例中的 3 例 (1.4%) 中，我们鉴定出导致常染色体显性中心性窝状脉络膜营养不良 (CACD) 的致病性杂合变异 (PRPH2 c.424C>T; p.R142W)。这些患者均表现为地图状萎缩。在 218 例病例中的 12 例 (5.5%) 中，我们鉴定出先前与常染色体显性黄斑营养不良症相关的基因中的杂合变异，其临床意义未知，但预测具有高度致病变异。仅根据眼底检查，区分 AMD 和类似 AMD 的营养不良症（如 CACD）可能具有挑战性。对与黄斑营养不良症相关的基因（特别是 PRPH2）进行遗传筛查有助于识别类似 AMD 的营养不良症。
