Expanding the Boundaries of RNA Sequencing as a Diagnostic Tool for Rare Mendelian Disease.

ABSTRACT: Gene-panel and whole-exome analyses are now standard methodologies for mutation detection in Mendelian disease. However, the diagnostic yield achieved is at best 50%, leaving the genetic basis for disease unsolved in many individuals. New approaches are thus needed to narrow the diagnostic gap. Whole-genome sequencing is one potential strategy, but it currently has variant-interpretation challenges, particularly for non-coding changes. In this study we focus on transcriptome analysis, specifically total RNA sequencing (RNA-seq), by using monogenetic neuromuscular disorders as proof of principle. We examined a cohort of 25 exome and/or panel "negative" cases and provided genetic resolution in 36% (9/25). Causative mutations were identified in coding and non-coding exons, as well as in intro

SUBMITTER: Gonorazky HD 

PROVIDER: S-EPMC6407525 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature