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

dc.rights.licenseopenen_US
dc.contributor.authorLAURIE, Steven
dc.contributor.authorSTEYAERT, Wouter
dc.contributor.authorDE BOER, Elke
dc.contributor.authorPOLAVARAPU, Kiran
dc.contributor.authorSCHUERMANS, Nika
dc.contributor.authorSOMMER, Anna K
dc.contributor.authorDEMIDOV, German
dc.contributor.authorELLWANGER, Kornelia
dc.contributor.authorPARAMONOV, Ida
dc.contributor.authorTHOMAS, Coline
dc.contributor.authorARETZ, Stefan
dc.contributor.authorBAETS, Jonathan
dc.contributor.authorBENETTI, Elisa
dc.contributor.authorBULLICH, Gemma
dc.contributor.authorCHINNERY, Patrick F
dc.contributor.authorCLAYTON-SMITH, Jill
dc.contributor.authorCOHEN, Enzo
dc.contributor.authorDANIS, Daniel
dc.contributor.authorDE SAINTE AGATHE, Jean-Madeleine
dc.contributor.authorDENOMMÉ-PICHON, Anne-Sophie
dc.contributor.authorDIAZ-MANERA, Jordi
dc.contributor.authorEFTHYMIOU, Stephanie
dc.contributor.authorFAIVRE, Laurence
dc.contributor.authorFERNANDEZ-CALLEJO, Marcos
dc.contributor.authorFREEBERG, Mallory
dc.contributor.authorGARCIA-PELAEZ, José
dc.contributor.authorGUILLOT-NOEL, Lena
dc.contributor.authorHAACK, Tobias B
dc.contributor.authorHANNA, Mike
dc.contributor.authorHENGEL, Holger
dc.contributor.authorHORVATH, Rita
dc.contributor.authorHOULDEN, Henry
dc.contributor.authorJACKSON, Adam
dc.contributor.authorJOHANSSON, Lennart
dc.contributor.authorJOHARI, Mridul
dc.contributor.authorKAMSTEEG, Erik-Jan
dc.contributor.authorKELLNER, Melanie
dc.contributor.authorKLEEFSTRA, Tjitske
hal.structure.identifierHôpital Pellegrin
hal.structure.identifierService de génétique médicale
hal.structure.identifierChercheur indépendant
hal.structure.identifierUniversité de Bordeaux [UB]
hal.structure.identifierCentre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]
hal.structure.identifierCHU de Bordeaux Pellegrin [Bordeaux]
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorLACOMBE, Didier
dc.contributor.authorLOCHMÜLLER, Hanns
dc.contributor.authorLÓPEZ-MARTÍN, Estrella
dc.contributor.authorMACAYA, Alfons
dc.contributor.authorMARCÉ-GRAU, Anna
dc.contributor.authorMAVER, Aleš
dc.contributor.authorMORSY, Heba
dc.contributor.authorMUNTONI, Francesco
dc.contributor.authorMUSACCHIA, Francesco
dc.contributor.authorNELSON, Isabelle
dc.contributor.authorNIGRO, Vincenzo
dc.contributor.authorOLIMPIO, Catarina
dc.contributor.authorOLIVEIRA, Carla
dc.contributor.authorPAULASOVÁ SCHWABOVÁ, Jaroslava
dc.contributor.authorPAULY, Martje G
dc.contributor.authorPETERLIN, Borut
dc.contributor.authorPETERS, Sophia
dc.contributor.authorPFUNDT, Rolph
dc.contributor.authorPILUSO, Giulio
dc.contributor.authorPISCIA, Davide
dc.contributor.authorPOSADA, Manuel
dc.contributor.authorREICH, Selina
dc.contributor.authorRENIERI, Alessandra
dc.contributor.authorRYBA, Lukas
dc.contributor.authorŠABLAUSKAS, Karolis
dc.contributor.authorSAVARESE, Marco
dc.contributor.authorSCHÖLS, Ludger
dc.contributor.authorSCHÜTZ, Leon
dc.contributor.authorSTEINKE-LANGE, Verena
dc.contributor.authorSTEVANIN, Giovanni
dc.contributor.authorSTRAUB, Volker
dc.contributor.authorSTURM, Marc
dc.contributor.authorSWERTZ, Morris A
dc.contributor.authorTARTAGLIA, Marco
dc.contributor.authorTE PASKE, Iris B A W
dc.contributor.authorTHOMPSON, Rachel
dc.contributor.authorTORELLA, Annalaura
dc.contributor.authorTRAINOR, Christina
dc.contributor.authorUDD, Bjarne
dc.contributor.authorVAN DE VONDEL, Liedewei
dc.contributor.authorVAN DE WARRENBURG, Bart
dc.contributor.authorVAN REEUWIJK, Jeroen
dc.contributor.authorVANDROVCOVA, Jana
dc.contributor.authorVITOBELLO, Antonio
dc.contributor.authorVOS, Janet
dc.contributor.authorVYHNÁLKOVÁ, Emílie
dc.contributor.authorWIJNGAARD, Robin
dc.contributor.authorWILKE, Carlo
dc.contributor.authorWILLIAM, Doreen
dc.contributor.authorXU, Jishu
dc.contributor.authorYALDIZ, Burcu
dc.contributor.authorZALATNAI, Luca
dc.contributor.authorZUREK, Birte
dc.contributor.authorBROOKES, Anthony J
dc.contributor.authorEVANGELISTA, Teresinha
dc.contributor.authorGILISSEN, Christian
dc.contributor.authorGRAESSNER, Holm
dc.contributor.authorHOOGERBRUGGE, Nicoline
dc.contributor.authorOSSOWSKI, Stephan
dc.contributor.authorRIESS, Olaf
dc.contributor.authorSCHÜLE, Rebecca
dc.contributor.authorSYNOFZIK, Matthis
dc.contributor.authorVERLOES, Alain
dc.contributor.authorMATALONGA, Leslie
dc.contributor.authorBRUNNER, Han G
dc.contributor.authorLOHMANN, Katja
dc.contributor.authorDE VOER, Richarda M
dc.contributor.authorTÖPF, Ana
dc.contributor.authorVISSERS, Lisenka E L M
dc.contributor.authorBELTRAN, Sergi
dc.contributor.authorHOISCHEN, Alexander
dc.date.accessioned2025-05-30T08:23:12Z
dc.date.available2025-05-30T08:23:12Z
dc.date.issued2025-01-17
dc.identifier.issn1546-170Xen_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/206781
dc.description.abstractEnGenetic 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.
dc.language.isoENen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.subject.enHumans
dc.subject.enRare Diseases
dc.subject.enEurope
dc.subject.enGenomics
dc.subject.enMale
dc.subject.enFemale
dc.subject.enPedigree
dc.subject.enDatabases
dc.subject.enGenetic
dc.subject.enGenetic Testing
dc.subject.enComputational Biology
dc.subject.enPolymorphism
dc.subject.enSingle Nucleotide
dc.subject.enGenetic Predisposition to Disease
dc.title.enGenomic reanalysis of a pan-European rare-disease resource yields new diagnoses.
dc.title.alternativeNat Meden_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1038/s41591-024-03420-wen_US
dc.subject.halSciences du Vivant [q-bio]/Génétiqueen_US
dc.identifier.pubmed39825153en_US
bordeaux.journalNature Medicineen_US
bordeaux.page478-489en_US
bordeaux.volume31en_US
bordeaux.hal.laboratoriesMaladies Rares : Génétique et Métabolisme (MRGM) - UMR 1211en_US
bordeaux.issue2en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcepubmed
hal.identifierhal-05090417
hal.version1
hal.date.transferred2025-05-30T08:23:29Z
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exporttrue
workflow.import.sourcepubmed
dc.rights.ccCC BY-NC-NDen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Nature%20Medicine&rft.date=2025-01-17&rft.volume=31&rft.issue=2&rft.spage=478-489&rft.epage=478-489&rft.eissn=1546-170X&rft.issn=1546-170X&rft.au=LAURIE,%20Steven&STEYAERT,%20Wouter&DE%20BOER,%20Elke&POLAVARAPU,%20Kiran&SCHUERMANS,%20Nika&rft.genre=article


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