Scaling genomic reanalysis to unlock diagnoses and transform rare disease care

N/A (large-scale systematic reanalysis program)

Analysis of factors determining diagnostic gain from large-scale genomic reanalysis: new variant/gene discoveries between initial test and reanalysis, database improvements (ClinVar, HGMD, OMIM), better HPO phenotype integration; case prioritization model for reanalysis

Large-scale study of the utility of systematic genomic reanalysis for undiagnosed rare disease cases. The article analyzes key determinants of diagnostic gain at reanalysis: new disease genes published between initial test and reanalysis, database updates (ClinVar, HGMD, OMIM), improved HPO phenotype integration, and new bioinformatics capabilities. A case prioritization model for reanalysis is proposed, allowing resources to be focused on cases with the highest resolution potential.

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

Systematic genomic reanalysis is one of the most cost-effective interventions in medical genetics: for pediatric NDD cases, new diagnosis rates of 10-25% are regularly reported at 2-3 years. The proposed prioritization model is directly applicable for structuring reanalysis programs in medical genomics centers.

HGG Advances (Cell Press) +2; large-scale data on reanalysis impact +3; case prioritization model +2; impact on lab organization +1