Scientists have provided a diagnosis for more than 500 European patients who did not know their condition. This work, which was performed by the Solving the Unsolved Rare Diseases (Solve-RD) consortium and was highly collaborative, has been reported in Nature Medicine.
In the European Union, a rare disorder is defined as one that occurs in fewer than five of 10,000 people. Genetic mutations are the cause of most of these rare disorders, but genetic sequencing cannot always provide an easy answer.
For this effort, the researchers analyzed genetic data that was already available for 6,447 affected individuals, and over 3,000 of their unaffected family members. The investigators also identified potential treatment options for about 15 percent of the 506 people who got a diagnosis.
The diseases that were identified covered a wide range of systems, and included neuromuscular disorders, intellectual disabilities, and neurological diseases.
This study has also outlined an approach for aiding patients with rare diseases, so that they can get a diagnosis and the right treatment when it is available. This methodology involves using multiple experts from various fields to improve the accuracy of diagnosis. The study authors noted that a reanalysis of existing genetic data can yield new results because sometimes, mutations that cause a disease have recently been identified, or annotated in databases. Usually, it takes money and time that is not available to perform these reanalyses, so they are often not done. But this research has shown the value of such reanalyses.
The work also highlights the advantages of advanced technologies like long-read genome sequencing, which can provide better coverage of genetic areas that are highly repetitive, for example; or RNA sequencing that assesses the transcripts of active genes rather than the genomic sequence, to accelerate the diagnoses of rare conditions.
"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 for a patient who has been ill for 20 years and has participated in many studies," said Lisenka Vissers, a Professor at Radboudumc.
"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," noted Alexander Hoischen, a Professor at Radboudumc.
Sources: Radboud University, Nature Medicine