Multimodal Sequencing and Reanalysis Approaches to End the Diagnostic Odyssey of Individuals with Suspected Rare Monogenic Diseases - PubMed
4 hours ago
- #genomic reanalysis
- #rare disease diagnosis
- #multimodal sequencing
- A multimodal reanalysis framework was evaluated for unsolved suspected monogenic disease families after prior testing.
- Six families were reviewed in weekly interdisciplinary conferences over one year using multiple sequencing and analysis methods.
- Three families (50%) achieved a molecular diagnosis, two (33%) had strong candidate findings, and one (17%) remained without definitive diagnosis.
- Resolved cases included variants in KLHL40, TTN, and RNU4-2, with functional transcriptomic analyses supporting some diagnoses.
- The study highlights that archived short-read data retain diagnostic value when reanalyzed with updated methods and knowledge.
- Adopting iterative, team-based multimodal strategies may help resolve complex unsolved rare-disease cases.