Challenges using diagnostic next-generation sequencing in the clinical environment for inherited retinal disorders

Abstract

Visual impairment, and in particular the inherited retinopathies, is a significant problem worldwide. Many disorders are progressive so their early and accurate detection is crucial to the development and application of appropriate disease management and treatment strategies, some of which are currently being tested in clinical trials. Over the past few decades, the identification of genetic causes that mediate many inherited diseases has largely been based on traditional 'Sanger sequencing' and microchip approaches that are expensive and time consuming. However, with the advent of next-generation sequencing it is now possible to apply high-throughput technologies to the clinical arena and sequence the entire exome or genome of an affected individual. Despite the potential for a paradigm shift in the clinical diagnosis of retinal disease, it may prove difficult to interpret and confirm the pathogenicity of any variants discovered by next-generation sequencing pipelines. In this review, I examine the application of next-generation sequencing to inherited retinal disorders and discuss current limitations and future perspectives.