Leicester experts contribute to international consortium helping patients with rare disease diagnosis

Experts from the University of Leicester have co-coordinated a European consortium of 300 researchers to help patients with unsolved rare diseases receive a diagnosis through new genetic reanalysis.  

More than 500 patients with unknown conditions have now received a diagnosis as part of the project, known as Solve-RD. 

This includes patients with rare neurological disorders, severe intellectual disabilities, muscle diseases, and hereditary gastrointestinal cancer. 

Diagnoses were achieved through the collaborative efforts of the researchers, led by researchers from the University of Tübingen, Germany, Radboud University Medical Center (UMC), in the Netherlands and the National Center for Genomic Analysis in Barcelona – with the University of Leicester co-coordinating this initiative. 

Experts from the University of Leicester also led the project’s IT efforts to create a data platform essential to its success. 

A disease is considered rare in the European Union if fewer than 5 out of 10,000 people have the condition. Of the 7,000 recognized rare diseases, at least 70% have a genetic cause. Because these diseases are so rare, it's difficult to pinpoint the exact cause in the DNA, even when multiple members of one family have the condition.

However, researchers were able to diagnose a number of European patients and families with their genetic rare disease thanks to the collaborative efforts taking place to improve and apply genetic testing in a consistent way across many thousands of rare disease cases. This meant that information could be unified and co-analysed based on inheritance patterns and similarities across disease features. 

To achieve this, the University of Leicester organized a collaboration of UK and European science teams to design and build a completely new data infrastructure for this level of data sharing and access, whilst also ensuring high quality and patient privacy.

Professor Anthony Brookes, from the University’s Department of Genetics, Genomics and Cancer Sciences, led the data systems work.

He said: “This advance is the result of over six years of hard work by many collaborating teams.

“Our efforts have proven that the immense complexities of rare genetic disease can yield to large-scale genetic and clinical data sharing and analysis. 

“Furthermore, now that we have the necessary data technologies in place, we have launched a new ‘European Rare Disease Research Alliance (ERDERA)’ project to replicate and apply these technologies to more patients and more areas of disease. This will provide ways for external researchers to find and safely examine the data.”

Specifically, the researchers reanalysed the existing genome data of 6,447 patients and 3,197 unaffected family members. Thanks to this research, 506 patients and their families received a diagnosis. For 15% of the patients, there are now leads for taking more action, including treatment, while other patients have received greater clarity on their condition. 

The results of the project have now been published in Nature Medicine. 

Thanks to the framework created by Solve-RD, it no longer matters whether a patient with a rare condition is seen in the UK, Netherlands, Germany, or France. The method for reaching a diagnosis is now the same everywhere with experts now agreed on the analysis method for each condition, for example, which genes and variant types need to be examined.

This structured approach allows diagnoses and potential treatment of rare diseases to be reviewed by experts from diverse fields, such as clinical genetics and data science, increasing diagnostic accuracy. 

Holm Graessner, Solve-RD coordinator said: “‘This a major step forward and a milestone for rare disease research in Europe. We will continue to scale up this approach in ERDERA to provide a diagnosis for even more patients and families across Europe.”

Lisenka Vissers, Professor in Translational Genomics and lead researcher from Radboud UMC said: “We conducted a large reanalysis of an enormous amount of patient data. This allowed us to find similarities and draw conclusions. We have now even been able to provide a diagnosis to a patient who has been ill for twenty years and has participated in many studies.”  

Alexander Hoischen, Professor in Genomic technologies for immune-mediated and infectious diseases and lead researcher from Radboud UMC, added: “The fact that we have achieved this is a unique example of the power of collaboration. It's a huge step forward in European cooperation, and this is just the beginning. Although we haven't made any new discoveries yet and these diagnoses come from existing data and analyses, we hope to be able to help many more patients in the coming years. Initially by making a diagnosis, but hopefully also with possible treatments.”