World first: Radboudumc pioneers new genetic test in clinical practice

Radboudumc is the first hospital in the world to use a new genetic test on a large scale in clinical practice. This test provides more people with a diagnosis for rare conditions and is faster and more efficient than current diagnostic methods. It can replace around fifteen other tests. 'This will become the new standard.'

For people with rare conditions, healthcare providers search for a genetic cause in their DNA. Together with Maastricht UMC+, Radboudumc is the first worldwide to introduce a new genetic test on a large scale in clinical settings. 'We’re starting with 5,000 tests per year, about one-sixth of the analyses we perform annually', says Helger IJntema, head of the Genome Diagnostics Laboratory. 'Initially, we’ll use the test for genetic forms of blindness and severe intellectual disabilities.'

The new test is based on so-called long-read genome sequencing. If a condition is potentially hereditary, the entire DNA of a patient is mapped—meaning all six billion building blocks found in every cell of our body. This is done by measuring small fragments of DNA and piecing them together. Just like with a jigsaw puzzle, assembling is much easier when the pieces are larger—hence, long-reads. This is now technically feasible and proven suitable for clinical use.

Building blocks

Research has shown that this new technique maps DNA much more completely than the method using short fragments. 'For some rare diseases, this leads to over ten percent more diagnoses', says Professor of Genomic Technologies Alexander Hoischen. 'Additionally, with this fully measured DNA, we can discover new hereditary causes for certain conditions. This could increase the percentage of additional diagnoses through research to as much as fifteen percent.'

The test also detects genetic errors that are hard to find. 'Sometimes a piece of DNA is copied to the wrong chromosome. With long-reads, this can be detected much more easily', says Professor of Translational Genomics Lisenka Vissers. Moreover, this technique not only visualizes the building blocks, but also various modifications to the DNA that can provide extra information about a condition. For example, certain chemical groups on the outside of DNA can switch genes on or off.

New standard

The new test provides patients with a diagnosis more frequently and more quickly. 'And that’s very important', says Professor of Care for Rare Diseases Wendy van Zelst-Stams, head of the Genetics Department at both Radboudumc and MUMC+. 'A diagnosis brings clarity and ends a long search. It often also provides a prognosis. People can connect with others in similar situations. For parents, it can relieve feelings of guilt. And we can assess risks if parents are considering having children.'

The Genome Diagnostics Laboratory also benefits from this test, that is now coming to the clinic thanks to a very large team. IJntema: 'Long read sequencing can replace fifteen other genetic tests in clinical practice, making diagnostics faster and more efficient.' Hoischen: 'I expect this will become the new standard for genome diagnostics and the only test we’ll perform in the future.'