New Long-Read Genome Sequencing Test Shows Higher Diagnostic Yield for Rare Genetic Disorders

New DNA Test Could Revolutionize Diagnosis of Rare Genetic Disorders

Researchers from Radboud University Medical Center (Radboudumc) and Maastricht University Medical Center+ (MUMC+) have developed a new DNA test that significantly improves diagnostic rates for rare genetic conditions. Using long-read genome sequencing, the test yields 3% more diagnoses than current standard methods and can replace up to fifteen other tests.

The findings, published in the New England Journal of Medicine, are so promising that the authors recommend adopting this test as the first-choice method for diagnosing rare genetic disorders.

"We showed that the new test yields three percent more diagnoses. It can also replace fifteen other tests. We recommend using this test worldwide as the first choice." — Professor Lisenka Vissers, Radboudumc

The study compared the new test with standard diagnostics in 1,000 patients. Traditional methods often require multiple, separate tests. In contrast, the new test uses long-read sequencing, which reads segments of up to 20,000 DNA building blocks at a time—compared to the 300-block fragments currently used.

A key advantage is that the new test also measures epigenetic modifications—chemical changes on the outside of DNA that can switch genes on or off. These modifications are sometimes the root cause of rare disorders, but standard diagnostics require separate, specialized tests to find them.

"With long reads we capture these modifications as a bonus—two in one." — Professor Christian Gilissen, Radboudumc

The new test provides a more complete picture of a patient's DNA, allowing doctors to detect complex abnormalities that are currently difficult to find. This capability was further demonstrated at the Undiagnosed Hackathon in Nijmegen, where nearly 150 specialists from Dutch university medical centers used the test to analyze DNA from 33 families. This collaboration resulted in five new diagnoses.

"Thanks to long reads, we obtain an even more complete view of DNA and can detect complex and hard-to-find abnormalities. We then link these to specific conditions. In this way, our knowledge grows and we can make more diagnoses." — Professor Alexander Hoischen, Radboudumc

A condition is classified as rare if it affects fewer than 1 in 2,000 people. There are over 7,000 different rare diseases, affecting up to 400 million people worldwide. Approximately 80% have a genetic cause.

Obtaining a diagnosis for a rare genetic disorder often takes years. A diagnosis can provide crucial clarity, a prognosis, connections with others who share the condition, and vital information for family planning. By offering a higher diagnostic yield in a single test, this breakthrough has the potential to shorten that long, difficult journey for countless patients.