Long-Read Sequencing Unearths Potentially Pathogenic Structural Variants in Blindness-Causing Disease

For a study appearing in the Journal of Medical Genetics, a research team based at centers in Japan turns to long-read sequencing to search for structural variants (SVs) that can explain mysterious retinitis pigmentosa cases. With Oxford Nanopore long-read sequencing of 15 retinitis pigmentosa patients, the investigators searched for pathogenic variants in several genes previously linked to retinitis pigmentosa, including the EYS gene, which has been implicated in autosomal recessive forms of retinitis pigmentosa in the past. In the process, the authors tracked down deletions impacting coding portions of the EYS gene in two of the 15 patients — alterations that did not appear to stem from founder mutations, based on their subsequent analyses on nearly 1,200 more cases. "In this study, we identified likely pathogenic SVs in two previously unsolved [retinitis pigmentosa] cases by long-read sequencing," the authors write, concluding that the current findings "imply that searching for SVs and the comprehensive evaluation of non-coding regions in genetically unsolved cases will contribute to the molecular diagnosis of [retinitis pigmentosa]."