Nature medicine · 2025

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

СтатьяНазвание и аннотация: Перевод в очереди

Обработка статьи · этапы, ошибки и управление

Загрузка состояния…

История · было → стало

Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.

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, Solve-RD DITF-GENTURIS, Solve-RD DITF-ITHACA, Solve-RD DITF-EURO-NMD, Solve-RD DITF-RND, Solve-RD consortium, 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

Аннотация

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.

Предметные рубрики MeSH

Humans Rare Diseases Europe Genomics Male Female Pedigree Databases, Genetic Genetic Testing Computational Biology Polymorphism, Single Nucleotide Genetic Predisposition to Disease

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

Ошибки и ограничения

Аннотация

Предметные рубрики MeSH