Progress and prospects of next-generation sequencing testing for inherited retinal dystrophy

Abstract

Next-generation sequencing, also known as massively paralleled sequencing, offers an unprecedented opportunity to study disease mechanisms of inherited retinal dystrophies: a dramatic change from a few years ago. The specific involvement of the retina and the manageable number of genes to sequence make inherited retinal dystrophies an attractive model to study genotype-phenotype correlations. Costs are reducing rapidly and the current overall mutation detection rate of approximately 60% offers real potential for personalized medicine and treatments. This report addresses the challenges ahead, which include: better understanding of the mutation mechanisms of syndromic genes in apparent non-syndromic patients; finding mutations in patients who have tested negative or inconclusive; better variant calling, especially for intronic and synonymous variants; more precise genotype-phenotype correlations and making genetic testing more broadly accessible.

Keywords: LCA; NGS; Stargardt disease; genes; genetic testing; genotyping; inherited retinal dystrophy; molecular diagnosis; retina; retinitis pigmentosa.