Long-read Genome Sequencing: The Next Revolution for Rare Diseases
The third session began with Prof. Dr. Alexander Hoischen from Radboud University Medical Center. The focus of his talk was the transition to what is known as long-read genome sequencing. This technology allows DNA to be analyzed in much longer fragments, enabling the detection of complex genetic changes that often remain hidden with traditional methods.
Hoischen emphasized that today’s diagnostics are reaching their limits. Despite advanced procedures, the genetic cause remains unclear for more than half of patients, often requiring several consecutive tests. This iterative approach is time-consuming and frequently delays a clear diagnosis.
New technologies could fundamentally change this situation. Studies show that additional diagnoses can be made and, in particular, complex variants can be detected much more accurately. Even cases previously analyzed can be retrospectively clarified. Clinical examples demonstrated that root genetic causes can still be identified after extensive diagnostics.
His outlook: In the long term, it should be possible to unite various diagnostic approaches into a comprehensive test, simplifying and accelerating diagnostics, and significantly improving care.
Connecting the Dots: Integrating Natural History, Patient Voices and Data
Next, Prof. Dr. Agnès Linglart from Université Paris-Saclay and Hôpital Bicêtre, highlighted how crucial structured data is for understanding and treating rare diseases. Using the rare metabolic disorder X-linked hypophosphatemia as an example, she explained how registries, cohorts, and long-term observations can provide a more comprehensive picture of the disease.
A shift in perspective also emerged. What was once considered solely a bone disorder is now understood as a lifelong, multisystemic disease. Particularly striking were the insights into the everyday reality of affected individuals. In addition to clinical parameters, aspects such as pain, reduced mobility, or dental problems are increasingly in focus as they significantly affect quality of life. Linglart stressed that only the systematic connection between clinical data, registries, and national databases allows better insight into disease progression and therapeutic effects. Different data sources complement each other, providing specific insights into care, progression, and treatment. However, this requires that data collection is targeted and guided by clear scientific questions.
Clinical and Research Frontiers in Rare Disease Genomics
Monica Wojcik MD, MPH, neonatologist and clinical geneticist at Boston Children’s Hospital, offered insights into current developments at the interface of research and clinical practice.
At the center was the work of the GREGoR Consortium, which advances genomic technologies and makes them usable for rare disease diagnosis. It was shown that, in particular, whole genome sequencing opens up additional diagnostic possibilities, such as for structural or complex genetic changes that are difficult to detect with other methods.
Another focus was on the combination of different data layers—known as multi-omics—where genomic data is linked with other molecular information such as RNA, protein, or metabolic analyses to better understand disease causes.
Of particular note were the insights into clinical practice. In neonatology, rapid sequencing techniques enable diagnoses within a few days, in some cases even within 48 hours, facilitating earlier and more targeted therapy choices. Development is moving toward ever-shorter analysis times and broader clinical implementation.
Wojcik also emphasized the importance of equitable access to these technologies. Certain population groups remain underrepresented in genetic research, which may limit the applicability of findings. The goal, she stated, is to make the potential of genomic medicine as broad and inclusive as possible.
Standards, Metadata and Interoperability: Making EHDS Work for Rare Disease Data
Dipak Kalra, President of the European Institute for Innovation through Health Data, discussed the role of the European Health Data Space in using health data for rare diseases.
The core question was how data can be made more accessible and usable across Europe, both for care and for research and innovation. The EHDS aims to provide a framework to facilitate health data sharing across country borders, while strengthening control and transparency for patients.
Kalra highlighted that the value of such data spaces depends critically on quality and interoperability. Harmonized standards, structured metadata, and shared formats are fundamental to meaningfully combine and analyze data. Only when data is semantically uniform and technically compatible can it be reliably used across systems. Using sensitive health data also requires clear and transparent access rules. Planned are structured access processes and secure analytics environments to enable data use while ensuring data protection.
His talk underscored that only the interplay of regulation, standards, and infrastructure unlocks the full potential of extensive health data spaces.
A Data Ecosystem for Rare Diseases: The Role of the Network of University Medicine
The final talk of the third session was by Ralf Heyder, head of the Coordination Office of the Network of University Medicine, on developing national data infrastructures for rare diseases.
He outlined the current situation, where data is often fragmented, isolated in disease-specific registries, and only partially linked. Clinical routine documentation gaps and differing requirements for research and data use make cross-location collaboration challenging. The Network of University Medicine (NUM) is creating an infrastructure in Germany to address these challenges.
The aim is to bring together clinical routine data, registries, biomaterials, and other data sources in an integrated, modular system usable for both research and care. Various data types and platforms are connected via common interfaces and gradually integrated into a robust data landscape.
Heyder emphasized that the main benefit of these data spaces lies in their networked nature. Only by connecting diverse data sources and applying common standards can broad analyses and new findings emerge. His presentation showed how national initiatives are advancing the construction of powerful data ecosystems—forming an essential basis for future research and care in the field of rare diseases.
The presentations of this third session illustrated how essential the interplay between technological innovation, data integration, and robust infrastructures is for the future of rare disease care.
Find insights into each session of the 10th Rare Disease Symposium here:
Keynote: From Silos to Systems: A Vision for the Future of Rare Disease Medicine
Session 1: Case Study Rare Obesity
Session 2: Collaboration Beyond Borders: Models That Work
Closing Lecture: Mapping Invisible Boundaries: The Ethics of Undiagnosed Lives in Rare Disease Research
Photos: Andrea Katheder
We extend heartfelt thanks to our partners for their support: KARL STORZ, Pfizer Pharma GmbH, Takeda Pharma Vertrieb GmbH & Co KG, Sanofi-Aventis Deutschland GmbH, Alexion Pharma Germany GmbH, Chiesi GmbH, Ipsen Pharma GmbH, UCB Pharma GmbH, PTC Therapeutics Germany GmbH and Roche Pharma.
