For decades, rare disease patients and their families have endured a painful “diagnostic odyssey,” bouncing between specialists and often going years without answers. Rare diseases, by definition, affect fewer than 5 in 10,000 people in the European Union, but with over 7,000 such conditions cataloged, their collective impact is profound. A staggering 70% of these diseases are genetic, yet pinpointing the precise DNA mutation responsible has often been a Herculean task. Now, thanks to an unprecedented pan-European collaboration and advances in big data analysis, hope is on the horizon for those with previously unsolved rare diseases.
The Problem: Challenges in Diagnosing Rare Diseases
Rare diseases are inherently elusive. Their rarity means that even geneticists often have limited knowledge about specific conditions. This is compounded by the complexity of our DNA, with millions of variants—many of which are harmless—making it difficult to identify the few that might cause disease. Adding to the challenge is the historical siloing of data: patient information, genetic analyses, and research findings have often been fragmented across different countries and institutions.
A Pan-European Big Data Solution
The Solve-RD project directly addresses these challenges, transforming how rare diseases are diagnosed through data integration and advanced bioinformatics. By pooling genomic data from across Europe into a unified resource, Solve-RD has redefined rare disease diagnostics.
The project aggregated data from 6,447 patients with unresolved rare diseases across 12 European countries and Canada, creating one of the most comprehensive rare disease genomic datasets globally. Researchers systematically reanalyzed this data using advanced bioinformatics tools, identifying structural variants, copy number variants, and rare mutations that were previously overlooked. Over 300 experts—clinicians, geneticists, and bioinformaticians—collaborated within European Reference Networks (ERNs), focusing on specific disease categories like neurological disorders and hereditary cancers.
Breakthrough Achievements
The study delivered 506 new diagnoses, representing 8.4% of the patient cohort, with an additional 4.1% identified through ad hoc expert reviews. This significant improvement demonstrates the power of reanalyzing genomic data with advanced methodologies, revealing previously undetected genetic variants and bringing hope to many in the rare disease community.
For 15% of patients, the findings provided actionable insights, including potential treatment options in some cases. Beyond therapies, these diagnoses offer families invaluable clarity, enabling them to understand their conditions and make informed decisions about care, while also providing a sense of closure and direction.
Many of the newly identified genetic variants had been overlooked due to limitations in earlier diagnostic pipelines or because the associated genes were not yet linked to known diseases. Advanced genomic reanalysis uncovered these variants, demonstrating how continuous reevaluation of data can lead to critical breakthroughs and deepen our understanding of rare diseases.
This progress was made possible through a standardized diagnostic framework applied across Europe. By ensuring uniform protocols and quality standards, the framework guarantees equal diagnostic care regardless of location—be it France, Spain, the Netherlands, or elsewhere. This harmonized approach underscores a pan-European commitment to equitable patient care and cutting-edge research.
From Solve-RD to ERDERA: Scaling the Revolution
The success of Solve-RD has laid the diagnostic groundwork for the European Rare Disease Research Alliance (ERDERA), a transformative initiative poised to revolutionize rare disease diagnosis, treatment and care on an even larger scale.
Building on the Solve-RD framework, ERDERA’s diagnostic work stream aims to reanalyze data for over 100,000 rare disease cases, creating the most extensive genomic resource of its kind. Advanced technologies, including long-read sequencing, optical genome mapping, and RNA sequencing, will uncover complex mutations undetectable by traditional methods. By unifying data collection, storage, and analysis standards, ERDERA ensures seamless collaboration across all 27 EU member states, democratizing access to cutting-edge diagnostics for smaller and less resourced countries.
Beyond rare diseases, ERDERA’s approach has the potential to transform healthcare systems, serving as a model for addressing systemic inequities and enhancing research and innovation. The scale of its dataset will fuel advancements in artificial intelligence, bioinformatics, and precision medicine, with benefits extending to more common conditions.
ERDERA offers a vision of a more inclusive healthcare system, eliminating geographic disparities to ensure, among others, equal access to diagnostic expertise and technologies. Its infrastructure supports underrepresented regions, while its innovations strengthen Europe’s leadership in rare disease research and position the EU as a global healthcare leader.
Read the press release to learn more and explore the full publication here.
