Integrative and systematic genomic approaches to improve diagnosis in rare and undiagnosed diseases: results from the RareBoost project.
Adding whole-genome and RNA sequencing solved half of previously undiagnosed rare disease cases, providing a replicable clinical pathway.
The RareBoost project applied an integrated, stepwise genomic strategy to 120 families with rare or undiagnosed diseases where conventional molecular testing had failed, achieving a combined 50.8% diagnostic and probable-diagnostic yield by adding genome sequencing, RNA-sequencing, and systematic data reanalysis to standard exome analysis. The tiered approach identified non-coding variants and resolved cases through RNA evidence, providing a scalable clinical framework replicable in any genomic medicine centre.
What the study was
- Study design
- prospective_cohort
- Category
- rare_diseases
- Maturity
- Validated
- Journal
- Eur J Hum Genet
Why it surfaced
European Journal of Human Genetics; directly addresses the diagnostic odyssey in rare/undiagnosed diseases; 50.8% composite yield in a previously negative cohort is clinically impactful; design_quality capped at 1 due to modest n=120 families and no control arm.
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