Evaluating genome sequencing strategies: trio, singleton, and standard testing in rare disease diagnosis
Our findings demonstrate that GS, particularly tGS, outperforms SoC in diagnosing rare diseases, with sGS providing a more cost-effective alternative. These results suggest that GS should be considered a first-tier genetic test, offering an efficient, single-step approach to reduce the diagnostic odyssey for patients with rare diseases. The trio approach proved especially valuable for less experienced teams, as inheritance data facilitated variant interpretation and maintained high diagnostic yield, while experienced teams achieved comparable results with singleton analysis alone.
Authors
- Imke Poggenburg
- Manuela Dittmar (ORCID: https://orcid.org/0000-0003-3862-7354)
- Christian Schlein (ORCID: https://orcid.org/0000-0002-2791-1790)
- Bernard Hoffmann
- Inga Nagel (ORCID: https://orcid.org/0000-0001-5174-4454)
- Verónica Yumiceba (ORCID: https://orcid.org/0000-0001-6998-7913)
- Andreas Recke (ORCID: https://orcid.org/0000-0002-7674-1804)
- Michael Salewski
- Juliane Köhler
- Hiltrud Muhle
- Lana Harder (ORCID: https://orcid.org/0009-0007-3507-6784)
- Saranya Balachandran (ORCID: https://orcid.org/0009-0002-4905-3093)
- Olaf Hiort (ORCID: https://orcid.org/0000-0001-7490-4983)
- Almuth Caliebe (ORCID: https://orcid.org/0000-0003-2157-425X)
- Janne Wehnert
- Yorck Hellenbroich
- Andreas Dalski
- Nadine Hornig (ORCID: https://orcid.org/0000-0003-2469-752X)
- Janina Fuß (ORCID: https://orcid.org/0000-0002-7631-9355)
- Varun K. A. Sreenivasan (ORCID: https://orcid.org/0000-0002-8667-8394)
- Bianca Greiten
- Alexander Maximilian Münchau (ORCID: https://orcid.org/0000-0002-3219-2284)
- Bettina Gehring
- Jelena Pozojevic (ORCID: https://orcid.org/0009-0001-1208-1122)
- Kathryn G. Roberts (ORCID: https://orcid.org/0000-0001-7626-4043)
- Malte Spielmann (ORCID: https://orcid.org/0000-0002-0583-4683)
- Irina Hüning
- Kristian Händler (ORCID: https://orcid.org/0000-0001-5273-5277)
- Gloria Herrmann
- Philip Rosenstiel (ORCID: https://orcid.org/0000-0002-9692-8828)
- Sandra Wilson (ORCID: https://orcid.org/0009-0006-4530-3154)
- Anna Möllring
- Kirstin Hoff (ORCID: https://orcid.org/0000-0002-3259-2536)
- Eva Maria Murga Penas (ORCID: https://orcid.org/0000-0003-1000-4286)
- Jasmin Lisfeld
- Rixa Woitschach
- Alexander E. Volk (ORCID: https://orcid.org/0000-0001-8505-0143)
- Sören Franzenburg (ORCID: https://orcid.org/0000-0001-6374-4910)
- Tobias Bäumer (ORCID: https://orcid.org/0000-0003-1014-1782)
- Britt-Sabina Löscher (ORCID: https://orcid.org/0000-0001-9022-9017)
- Christina M. Post (ORCID: https://orcid.org/0000-0001-8133-9273)
- Britta Hanker
- Norbert Brüggemann (ORCID: https://orcid.org/0000-0001-5969-6899)
- Nils G. Margraf (ORCID: https://orcid.org/0000-0003-2197-1079)
- Louiza Toutouna (ORCID: https://orcid.org/0009-0008-8608-5127)
- Theresia Herget (ORCID: https://orcid.org/0009-0005-5035-9534)
- Dzhoy Papingi
- Amelie T. van der Ven (ORCID: https://orcid.org/0000-0002-4167-8411)
- Daniel Kaschta (ORCID: https://orcid.org/0009-0004-8128-5024)
- Andre Franke
- Inga Vater
- Christine Zühlke
- V. Berge
- Katharina Schau-Römer
- Franka Rust
- Laelia Rösler
- Franziska Gaass
- Friederike Birgel
- Anna-Sophie Liegmann
- Rebecca Gembicki
- Michelle Meyenborg
- Monika Kautza-Lucht
- Vincent Arriens
- Caroline Utermann-Thüsing
- Henning Nommels
- Milad Al-Tawil
- Kristin Grohte
Institutions
- Witten/Herdecke University (DE)
- Universität Hamburg (DE)
- University of Freiburg (DE)
- University of Zurich (CH)
- University Medical Center Freiburg (DE)
- Christian-Albrechts-Universität zu Kiel (DE)
- German Center for Pediatric and Adolescent Rheumatology (DE)
- Klinikum Itzehoe (DE)
- University Medical Center Hamburg-Eppendorf (DE)
- University Hospital Schleswig-Holstein (DE)
- Klinikum Lüneburg (DE)
- German Centre for Cardiovascular Research (DE)
- University of Lübeck (DE)
Publication Details
- Journal
- Genome Medicine
- Published
- 2025-09-17
- DOI
- https://doi.org/10.1186/s13073-025-01516-7
- Citations
- 5
- Primary Topic
- Genomics and Rare Diseases
- Type
- article
- Field-Weighted Citation Impact
- 9.09
Funders
- Deutsches Zentrum für Herz-Kreislaufforschung
- Deutsche Forschungsgemeinschaft