Professor Alexander Hoischen and his team at Radboud University Medical Center in Nijmegen have cracked open a faster path to answers for families lost in the labyrinth of rare disease diagnosis. Their breakthrough: a single DNA test that can replace 15 others and catches 3% more diagnoses than the patchwork of standard diagnostics most patients endure today.
The stakes are staggering. Around 400 million people worldwide live with a rare disease—one that affects fewer than 1 in 2,000 people—and 80% of these conditions have a genetic root. Yet diagnosis often takes years. That delay is not merely frustrating; it steals clarity, delays access to support networks and specialist care, and leaves families in the dark about reproductive risks. A diagnosis changes everything.
The research, published in the New England Journal of Medicine, involved 1,000 patients and a collaboration between Radboud and Maastricht UMC+. The team compared current standard diagnostics—which typically require multiple fragmented tests—against a new approach called long-read genome sequencing. The difference lies in the scale of DNA segments the test examines. Traditional methods read fragments of about 300 DNA building blocks, then laboriously stitch them together like a jigsaw puzzle with tiny pieces. Long-read sequencing reads segments up to 20,000 building blocks long. Larger pieces mean a clearer, more complete picture.
But the innovation runs deeper. The test does something standard diagnostics cannot easily do: it reads not only the DNA building blocks themselves but also modifications on the DNA's outer surface. These epigenetic markers can switch genes on or off and sometimes cause rare disorders. As Professor of Genome Bioinformatics Christian Gilissen explains, capturing these modifications usually demands additional specialized tests. Long-read sequencing captures them as a "2 in 1"—efficiency and completeness rolled into one.
"We showed that the new test yields 3% more diagnoses. It can also replace 15 other tests. We recommend using this test worldwide as the first choice," says Professor of Translational Genomics Lisenka Vissers. The implication is profound: faster diagnosis, lower costs, and better outcomes for families desperate for answers.
The promise extends beyond the study. Professor Alexander Hoischen notes that diagnoses are expected to rise further as researchers link newly discovered genetic abnormalities to specific conditions. Knowledge compounds; as the field grows, so does the ability to identify disease.
This potential came alive at the recent Undiagnosed Hackathon in Nijmegen, where nearly 150 specialists from all Dutch university medical centers gathered to tackle 33 families without a diagnosis. Armed with long-read sequencing and collective expertise, they achieved five new diagnoses in a single intensive session—proof that the test works not only in isolation but as a catalyst for discovery when paired with specialist knowledge.
Researchers have already submitted recommendations that this test be adopted worldwide as the first diagnostic choice for rare genetic disorders. For the millions searching for answers, it signals a turning point: a technology that finally makes the DNA puzzle easier to solve.