Genomic Research as a Critical Pathway to Diagnosis for Individuals with Rare Disease

The Rare Genomes Project (RGP) provides remote research-based genomic sequencing service for families with rare diseases to overcome diagnostic barriers. Since 2017, the project enrolled clinically heterogeneous, undiagnosed rare disease families from all fifty US states, Washington DC, and Puerto Rico. Results were returned to 272 of 1014 sequenced families, achieving a solve rate of 23.3% and a returned strong candidate rate of 3.5%. Condition-specific return rates ranged from 15% to 40%. Research interventions contributed to results in 16% of all families and included variants in recently discovered genes or non-coding regions. The study demonstrates that a research-driven, patient-centered sequencing project can effectively bridge the diagnostic gap for rare disease families underserved by current clinical care.