Abstract
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.
Highlights
Age-related macular degeneration (AMD) is a common progressive retinal disorder affecting the elderly.[1]
3.1 | Variants in genes associated with autosomal dominant macular dystrophies
We identified a heterozygous variant in the PRPH2 gene (c.424C > T, p.Arg142Trp) in three (1.4%) of 218 patients
Summary
Age-related macular degeneration (AMD) is a common progressive retinal disorder affecting the elderly.[1]. Therapies targeting AMD disease pathways are currently being evaluated in clinical trials.[3,4]. Sometimes it is clinically challenging to distinguish AMD from inherited macular dystrophies.[5,6,7] Especially when a patient presents at older age and GA has already developed, it can be challenging to distinguish AMD from GA secondary to other macular diseases and potentially patients might be misdiagnosed. Before inclusion of patients in clinical trials for dry AMD, it may be useful to perform genetic testing to exclude AMD-mimicking dystrophies. We evaluated the occurrence of rare genetic variants associated with autosomal dominant or autosomal. Known pathogenic variants associated with autosomal dominant macular dystrophy (Figure 1)
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