Stratified evaluation of blood RNA sequencing in a rare disease cohort

Whole blood RNA-seq, stratification by VUS splicing type, 32.9% diagnostic yield

This study evaluates whole blood RNA-seq in 90 patients with suspected Mendelian disease after non-diagnostic exome sequencing, stratifying them into 3 groups: splicing VUS identified, pre-diagnosis available, and no diagnosis. Overall diagnostic yield reaches 32.9%, with superior performance in the splicing VUS group (50%). Deep intronic variants, pseudo-exons, and somatic mosaic events are detected in DNA-only-unresolved cases, confirming the added value of the transcriptomic approach in the diagnostic odyssey.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Patient stratification before RNA-seq is the key contribution: it optimizes resource use and identifies which subgroups benefit most. A 50% yield in patients with splicing VUS is a strong argument for RNA-seq implementation in laboratories handling neuromuscular diseases and mitochondrial dysfunction.

Clinical impact: 3/3 · Evidence strength: 3/3 · Novelty: 1/2 · Sample size: 1/1 · Publication status: 0/1 → Total: 8/10