LAURIE, Steven; STEYAERT, Wouter; DE BOER, Elke; POLAVARAPU, Kiran; SCHUERMANS, Nika; SOMMER, Anna K; DEMIDOV, German; ELLWANGER, Kornelia; PARAMONOV, Ida; THOMAS, Coline; ARETZ, Stefan; BAETS, Jonathan; BENETTI, Elisa; BULLICH, Gemma; CHINNERY, Patrick F; CLAYTON-SMITH, Jill; COHEN, Enzo; DANIS, Daniel; DE SAINTE AGATHE, Jean-Madeleine; DENOMMÉ-PICHON, Anne-Sophie; DIAZ-MANERA, Jordi; EFTHYMIOU, Stephanie; FAIVRE, Laurence; FERNANDEZ-CALLEJO, Marcos; FREEBERG, Mallory; GARCIA-PELAEZ, José; GUILLOT-NOEL, Lena; HAACK, Tobias B; HANNA, Mike; HENGEL, Holger; HORVATH, Rita; HOULDEN, Henry; JACKSON, Adam; JOHANSSON, Lennart; JOHARI, Mridul; KAMSTEEG, Erik-Jan; KELLNER, Melanie; KLEEFSTRA, Tjitske; LACOMBE, Didier; LOCHMÜLLER, Hanns; LÓPEZ-MARTÍN, Estrella; MACAYA, Alfons; MARCÉ-GRAU, Anna; MAVER, Aleš; MORSY, Heba; MUNTONI, Francesco; MUSACCHIA, Francesco; NELSON, Isabelle; NIGRO, Vincenzo; OLIMPIO, Catarina; OLIVEIRA, Carla; PAULASOVÁ SCHWABOVÁ, Jaroslava; PAULY, Martje G; PETERLIN, Borut; PETERS, Sophia; PFUNDT, Rolph; PILUSO, Giulio; PISCIA, Davide; POSADA, Manuel; REICH, Selina; RENIERI, Alessandra; RYBA, Lukas; ŠABLAUSKAS, Karolis; SAVARESE, Marco; SCHÖLS, Ludger; SCHÜTZ, Leon; STEINKE-LANGE, Verena; STEVANIN, Giovanni; STRAUB, Volker; STURM, Marc; SWERTZ, Morris A; TARTAGLIA, Marco; TE PASKE, Iris B A W; THOMPSON, Rachel; TORELLA, Annalaura; TRAINOR, Christina; UDD, Bjarne; VAN DE VONDEL, Liedewei; VAN DE WARRENBURG, Bart; VAN REEUWIJK, Jeroen; VANDROVCOVA, Jana; VITOBELLO, Antonio; VOS, Janet; VYHNÁLKOVÁ, Emílie; WIJNGAARD, Robin; WILKE, Carlo; WILLIAM, Doreen; XU, Jishu; YALDIZ, Burcu; ZALATNAI, Luca; ZUREK, Birte; BROOKES, Anthony J; EVANGELISTA, Teresinha; GILISSEN, Christian; GRAESSNER, Holm; HOOGERBRUGGE, Nicoline; OSSOWSKI, Stephan; RIESS, Olaf; SCHÜLE, Rebecca; SYNOFZIK, Matthis; VERLOES, Alain; MATALONGA, Leslie; BRUNNER, Han G; LOHMANN, Katja; DE VOER, Richarda M; TÖPF, Ana; VISSERS, Lisenka E L M; BELTRAN, Sergi; HOISCHEN, Alexander

doi:10.1038/s41591-024-03420-w

Langue

Article de revue

Ce document a été publié dans

Nature Medicine. 2025-01-17, vol. 31, n° 2, p. 478-489

Résumé en anglais

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.< Réduire

Mots clés en anglais

Humans

Rare Diseases

Europe

Genomics

Male

Female

Pedigree

Databases

Genetic

Genetic Testing

Computational Biology

Polymorphism

Single Nucleotide

Genetic Predisposition to Disease

URI

https://oskar-bordeaux.fr/handle/20.500.12278/206781

DOI

http://dx.doi.org/10.1038/s41591-024-03420-w

Unités de recherche

Maladies Rares : Génétique et Métabolisme (MRGM) - UMR 1211

Voir/Ouvrir

Métadonnées

Partager cette publication !

Licence d’utilisation du document

Genomic reanalysis of a pan-European rare-disease resource yields new diagnoses.

Langue

Ce document a été publié dans

Résumé en anglais

Mots clés en anglais

URI

DOI

Unités de recherche