ArticleNature medicine2025
Genomic reanalysis of a pan-European rare-disease resource yields new diagnoses.
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Article in Nature medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 44 papers, 1 of them a synthesis that pooled it.
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44citing papers in PubMed, 1 pooled it
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it.
- 46,XY DSD with Partial Gonadal Dysgenesis and Growth Failure in a Patient with 3q27.1 Microdeletion: Candidate Gene Curation After Exhaustive Literature Review.International journal of molecular sciences · 2026Pooled it
- Consensus recommendations for next-generation sequencing-based genetic testing in Rare Neurological diseases.European journal of human genetics : EJHG · 2026Article
- Caring for Rare Genetic Disease: A Vision for the Future.Journal of genetic counseling · 2026Article
- Integrative and systematic genomic approaches to improve diagnosis in rare and undiagnosed diseases: results from the RareBoost project.European journal of human genetics : EJHG · 2026Article
- Genomic Strategies in Pediatric Care: Addressing Rare Diseases in Children.Children (Basel, Switzerland) · 2026Review
- Exploring needs and priorities in digital health management for rare disease patients and their caregivers: A mixed-methods study.PLOS digital health · 2026Article
- aiDIVA - hybrid AI for rare disease diagnostics using evidence-based, machine learning and language models.NPJ genomic medicine · 2026Article
- Automated reanalysis of genomic data for rare disease diagnostics at scale.Nature medicine · 2026Article
- Best practice recommendations for bioinformatics approaches applied to high-throughput sequencing for rare disease and cancer diagnosis within the UK National Health Service.Journal of medical genetics · 2026Article
- Systematic reanalysis of next-generation sequencing data in 101 neuromuscular disorder families enhances diagnostic yield, reveals intronic variants, and identifies a novel disease gene.Journal of neurology · 2026Article
- Advancing the diagnosis of rare neuromuscular and neurological diseases through the collaborative Solve-RD research framework.Journal of neuromuscular diseases · 2026Review
- Collaborative Genomics for Dystonia in Central and Eastern Europe: Successes Achieved, New Frontiers Ahead.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- The importance and clinical utility of reanalysis of exome and genome sequencing data.Kidney research and clinical practice · 2026Article
- Genotypic and phenotypic spectrum of Galloway-Mowat syndrome in Kuwait.Global medical genetics · 2026Article
- Fibroblast Transcriptomics in Molecular Diagnostics of a Comprehensive Dystonia Cohort.Annals of neurology · 2026Article
- Mapping functional non-coding variation in individual human genomes through haplotyping, multiomics, and deep learning.Nature communications · 2026Article
- Article
- Genome Sequencing of Undiagnosed European Patients Suspected of Hereditary Cancer: Diagnostic Yield and Identification of Candidate Causative Variants.JCO precision oncology · 2026Article
- Biallelic variants in RNU2-2 cause a remarkably frequent developmental and epileptic encephalopathy.Nature genetics · 2026Article
- The Potential of Digital Twins for Pediatric Rare Diseases.CPT: pharmacometrics & systems pharmacology · 2026Review
Corrections and comments
- Erratum issued
Authors and funding
114 authors.
Steven Laurie *Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain.
Wouter Steyaert *Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Elke de Boer *Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Kiran Polavarapu *Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.ORCID http://orcid.org/0000-0002-8879-6001
Nika Schuermans *Program for Undiagnosed Rare Diseases (UD-PrOZA), Ghent University Hospital, Ghent, Belgium.
Anna K Sommer *Institute of Human Genetics, Medical Faculty, University of Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0001-6850-9290
German DemidovInstitute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.
Kornelia EllwangerInstitute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.ORCID http://orcid.org/0000-0003-4845-5795
Ida ParamonovCentro Nacional de Análisis Genómico (CNAG), Barcelona, Spain.
Coline ThomasEuropean Bioinformatics Institute, European Molecular Biology Laboratory, Cambridge, UK.
Stefan AretzInstitute of Human Genetics, Medical Faculty, University of Bonn, Bonn, Germany.
Jonathan BaetsTranslational Neurosciences, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
Elisa BenettiMed Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy.ORCID http://orcid.org/0000-0002-0819-604X
Gemma BullichCentro Nacional de Análisis Genómico (CNAG), Barcelona, Spain.ORCID http://orcid.org/0000-0002-0737-4422
Patrick F ChinneryDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Jill Clayton-SmithDivision of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Enzo CohenCentre de Recherche en Myologie, Sorbonne Université, Inserm, Institut de Myologie, Paris, France.
Daniel DanisJackson Laboratory for Genomic Medicine, Farmington, CT, USA.ORCID http://orcid.org/0000-0003-0900-3411
Jean-Madeleine de Sainte AgatheDepartment of Genetics, Assistance Publique-Hôpitaux de Paris, Sorbonne Université, Pitié-Salpêtrière University Hospital, Paris, France.ORCID http://orcid.org/0000-0002-7753-8226
Anne-Sophie Denommé-PichonUniversity of Burgundy, Dijon, France.ORCID http://orcid.org/0000-0002-8986-8222
Jordi Diaz-ManeraJohn Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.ORCID http://orcid.org/0000-0003-2941-7988
Stephanie EfthymiouDepartment of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.ORCID http://orcid.org/0000-0003-4900-9877
Laurence FaivreUniversity of Burgundy, Dijon, France.
Marcos Fernandez-CallejoCentro Nacional de Análisis Genómico (CNAG), Barcelona, Spain.
Mallory FreebergEuropean Bioinformatics Institute, European Molecular Biology Laboratory, Cambridge, UK.ORCID http://orcid.org/0000-0003-2949-3921
José Garcia-PelaezInstituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
Lena Guillot-NoelInstitut du Cerveau, Sorbonne University, Paris, France.ORCID http://orcid.org/0000-0002-0287-3361
Tobias B HaackInstitute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.ORCID http://orcid.org/0000-0001-6033-4836
Mike HannaMRC Centre for Neuromuscular Diseases and National Hospital for Neurology and Neurosurgery, UCL Queen Square Institute of Neurology, London, UK.
Holger HengelDepartment of Neurodegeneration, Hertie Institute for Clinical Brain Research (HIH), University of Tübingen, Tübingen, Germany.ORCID http://orcid.org/0000-0002-9773-2667
Rita HorvathDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-9841-170X
Henry HouldenDepartment of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.ORCID http://orcid.org/0000-0002-2866-7777
Adam JacksonDivision of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Lennart JohanssonDepartment of Genetics, Genomics Coordination Center, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.ORCID http://orcid.org/0000-0002-4914-3737
Mridul JohariFolkhälsan Research Centre and Medicum, University of Helsinki, Helsinki, Finland.
Erik-Jan KamsteegDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Melanie KellnerDepartment of Neurodegeneration, Hertie Institute for Clinical Brain Research (HIH), University of Tübingen, Tübingen, Germany.
Tjitske KleefstraDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Didier LacombeMRGM, Maladies Rares: Génétique et Métabolisme, INSERM U1211, Université de Bordeaux, Bordeaux, France.
Hanns LochmüllerCentro Nacional de Análisis Genómico (CNAG), Barcelona, Spain.ORCID http://orcid.org/0000-0003-2324-8001
Estrella López-MartínInstitute of Rare Diseases Research, Spanish Undiagnosed Rare Diseases Cases Program (SpainUDP) & Undiagnosed Diseases Network International (UDNI), Instituto de Salud Carlos III, Madrid, Spain.ORCID http://orcid.org/0000-0003-3212-1424
Alfons MacayaPediatric Neurology Research Group, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain.
Anna Marcé-GrauPediatric Neurology Research Group, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain.ORCID http://orcid.org/0000-0001-5762-4023
Aleš MaverClinical Institute of Genomic Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Heba MorsyDepartment of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.
Francesco MuntoniDubowitz Neuromuscular Centre, UCL Great Ormond Street Hospital, London, UK.ORCID http://orcid.org/0000-0002-9102-5232
Francesco MusacchiaDipartimento di Medicina di Precisione, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy.
Isabelle NelsonCentre de Recherche en Myologie, Sorbonne Université, Inserm, Institut de Myologie, Paris, France.
Vincenzo NigroDipartimento di Medicina di Precisione, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy.
Catarina OlimpioDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-0112-5767
Carla OliveiraIPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.ORCID http://orcid.org/0000-0001-8340-2264
Jaroslava Paulasová SchwabováCentre of Hereditary Ataxia, Department of Neurology, Charles University Prague-2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
Martje G PaulyInstitute of Systems Motor Science, University of Lübeck, Lübeck, Germany.ORCID http://orcid.org/0000-0002-7794-0282
Borut PeterlinClinical Institute of Genomic Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Sophia PetersInstitute of Human Genetics, Medical Faculty, University of Bonn, Bonn, Germany.
Rolph PfundtDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Giulio PilusoDipartimento di Medicina di Precisione, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy.ORCID http://orcid.org/0000-0001-9418-125X
Davide PisciaCentro Nacional de Análisis Genómico (CNAG), Barcelona, Spain.
Manuel PosadaInstitute of Rare Diseases Research, Spanish Undiagnosed Rare Diseases Cases Program (SpainUDP) & Undiagnosed Diseases Network International (UDNI), Instituto de Salud Carlos III, Madrid, Spain.
Selina ReichDepartment of Neurodegeneration, Hertie Institute for Clinical Brain Research (HIH), University of Tübingen, Tübingen, Germany.
Alessandra RenieriMed Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy.ORCID http://orcid.org/0000-0002-0846-9220
Lukas RybaDepartment of Biology and Medical Genetics, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
Karolis ŠablauskasDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Marco SavareseFolkhälsan Research Centre and Medicum, University of Helsinki, Helsinki, Finland.
Ludger SchölsDepartment of Neurodegeneration, Hertie Institute for Clinical Brain Research (HIH), University of Tübingen, Tübingen, Germany.
Leon SchützInstitute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.
Verena Steinke-LangeMedizinische Klinik und Poliklinik IV - Campus Innenstadt, Klinikum der Universität München, Munich, Germany.
Giovanni StevaninInstitut du Cerveau, Sorbonne University, Paris, France.
Volker StraubJohn Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.ORCID http://orcid.org/0000-0001-9046-3540
Marc SturmInstitute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.ORCID http://orcid.org/0000-0002-6552-8362
Morris A SwertzDepartment of Genetics, Genomics Coordination Center, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Marco TartagliaMolecular Genetics and Functional Genomics, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy.ORCID http://orcid.org/0000-0001-7736-9672
Iris B A W Te PaskeDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Rachel ThompsonChildren's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
Annalaura TorellaDipartimento di Medicina di Precisione, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy.
Christina TrainorJohn Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Bjarne UddFolkhälsan Research Centre and Medicum, University of Helsinki, Helsinki, Finland.
Liedewei Van de VondelTranslational Neurosciences, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
Bart van de WarrenburgDonders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
Jeroen van ReeuwijkDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.ORCID http://orcid.org/0000-0002-0658-4399
Jana VandrovcovaDepartment of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.
Antonio VitobelloUniversity of Burgundy, Dijon, France.
Janet VosDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Emílie VyhnálkováDepartment of Biology and Medical Genetics, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
Robin WijngaardDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Carlo WilkeDepartment of Neurodegeneration, Hertie Institute for Clinical Brain Research (HIH), University of Tübingen, Tübingen, Germany.
Doreen WilliamInstitute of Clinical Genetics, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany.ORCID http://orcid.org/0000-0001-7824-5073
Jishu XuInstitute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.
Burcu YaldizDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Luca ZalatnaiCentro Nacional de Análisis Genómico (CNAG), Barcelona, Spain.
Birte ZurekInstitute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.
Solve-RD DITF-GENTURIS
Solve-RD DITF-ITHACA
Solve-RD DITF-EURO-NMD
Solve-RD DITF-RND
Solve-RD consortium
Anthony J BrookesDepartment of Genetics and Genome Biology, University of Leicester, Leicester, UK.ORCID http://orcid.org/0000-0001-8686-0017
Teresinha EvangelistaCentre de Recherche en Myologie, Sorbonne Université, Inserm, Institut de Myologie, Paris, France.ORCID http://orcid.org/0000-0002-1329-9131
Christian GilissenDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.ORCID http://orcid.org/0000-0003-1693-9699
Holm GraessnerInstitute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.
Nicoline HoogerbruggeDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Stephan OssowskiInstitute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.ORCID http://orcid.org/0000-0002-7416-9568
Olaf RiessInstitute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.
Rebecca SchüleDepartment of Neurodegeneration, Hertie Institute for Clinical Brain Research (HIH), University of Tübingen, Tübingen, Germany.
Matthis SynofzikDepartment of Neurodegeneration, Hertie Institute for Clinical Brain Research (HIH), University of Tübingen, Tübingen, Germany.ORCID http://orcid.org/0000-0002-2280-7273
Alain VerloesDept of Genetics, Assistance Publique-Hôpitaux de Paris, Université de Paris, Robert DEBRE University Hospital, Paris, France.ORCID http://orcid.org/0000-0003-4819-0264
Leslie MatalongaCentro Nacional de Análisis Genómico (CNAG), Barcelona, Spain.
Han G BrunnerDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Katja LohmannInstitute of Neurogenetics, University of Lübeck, Lübeck, Germany.ORCID http://orcid.org/0000-0002-5121-1460
Richarda M de VoerDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Ana TöpfJohn Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Lisenka E L M VissersDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Sergi BeltranCentro Nacional de Análisis Genómico (CNAG), Barcelona, Spain.ORCID http://orcid.org/0000-0002-2810-3445
Alexander HoischenDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.ORCID http://orcid.org/0000-0002-8072-4476
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genetic diagnosis of rare diseases requires accurate identification and interpretation of genomic variants. Clinical and molecular scientists from 37 expert centers across Europe created the Solve-Rare Diseases Consortium (Solve-RD) resource, encompassing clinical, pedigree and genomic rare-disease data (94.5% exomes, 5.5% genomes), and performed systematic reanalysis for 6,447 individuals (3,592 male, 2,855 female) with previously undiagnosed rare diseases from 6,004 families. We established a collaborative, two-level expert review infrastructure that allowed a genetic diagnosis in 506 (8.4%) families. Of 552 disease-causing variants identified, 464 (84.1%) were single-nucleotide variants or short insertions/deletions. These variants were either located in recently published novel disease genes (n = 67), recently reclassified in ClinVar (n = 187) or reclassified by consensus expert decision within Solve-RD (n = 210). Bespoke bioinformatics analyses identified the remaining 15.9% of causative variants (n = 88). Ad hoc expert review, parallel to the systematic reanalysis, diagnosed 249 (4.1%) additional families for an overall diagnostic yield of 12.6%. The infrastructure and collaborative networks set up by Solve-RD can serve as a blueprint for future further scalable international efforts. The resource is open to the global rare-disease community, allowing phenotype, variant and gene queries, as well as genome-wide discoveries.
Indexed as
GenomicsRare DiseasesComputational BiologyDatabases, GeneticEuropeFemaleGenetic Predisposition to DiseaseGenetic TestingHumansMalePedigreePolymorphism, Single Nucleotide
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