Solving unsolved rare neurological diseases-a Solve-RD viewpoint

Matalonga, Leslie; Timmann, Dagmar; Erasmus, Corrie E.; Reichbauer, Jennifer; Wayand, Melanie; Solve-RD-DITF-RND; van de Warrenburg, Bart; Schöls, Ludger; Wilke, Carlo; Bevot, Andrea; Zuchner, Stephan; Beltran, Sergi; Laurie, Steven, 1973-; Graessner, Holm; Synofzik, Matthis; Solve-RD Consortium

Solving unsolved rare neurological diseases-a Solve-RD viewpoint

Mostra el registre complet Registre parcial de l'ítem

dc.contributor.author Matalonga, Leslie
dc.contributor.author Timmann, Dagmar
dc.contributor.author Erasmus, Corrie E.
dc.contributor.author Reichbauer, Jennifer
dc.contributor.author Wayand, Melanie
dc.contributor.author Solve-RD-DITF-RND
dc.contributor.author van de Warrenburg, Bart
dc.contributor.author Schöls, Ludger
dc.contributor.author Wilke, Carlo
dc.contributor.author Bevot, Andrea
dc.contributor.author Zuchner, Stephan
dc.contributor.author Beltran, Sergi
dc.contributor.author Laurie, Steven, 1973-
dc.contributor.author Matalonga, Leslie
dc.contributor.author Graessner, Holm
dc.contributor.author Synofzik, Matthis
dc.contributor.author Solve-RD Consortium
dc.date.accessioned 2021-06-30T10:21:47Z
dc.date.available 2021-06-30T10:21:47Z
dc.date.issued 2021
dc.description.abstract Rare genetic neurological disorders (RND; ORPHA:71859) are a heterogeneous group of disorders comprising >1700 distinct genetic disease entities. However, genetic discoveries have not yet translated into dramatic increases of diagnostic yield and indeed rates of molecular genetic diagnoses have been stuck at about 30–50% across NGS modalities and RND phenotypes [1, 2]. Existence of yet unknown disease genes as well as shortcomings of commonly employed NGS technologies and analysis pipelines in detecting certain variant types are typically cited to explain the low diagnosis rates. To increase the diagnostic yield in RNDs - one of the four focus disease groups in Solve-RD - we follow two major approaches, that we will here present and exemplify: (i) systematic state-of the art re-analysis of large cohorts of unsolved whole-exome/genome sequencing (WES/WGS) RND datasets; and (ii) novel-omics approaches. Based on the way Solve-RD systematically organizes researchers’ expertise to channel this approach [3], the European Reference Network for Rare Neurological Diseases (ERN-RND) has established its own Data Interpretation Task Force (DITF) within SOLVE-RD, which is currently composed of clinical and genetic experts from 29 sites in 15 European countries.
dc.description.sponsorship The Solve-RD project has received funding from the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No. 779257. Data were analysed using the RD‐Connect Genome‐Phenome Analysis Platform, which received funding from EU projects RD‐Connect, Solve-RD and EJP-RD (Grant Numbers FP7 305444, H2020 779257, H2020 825575), Instituto de Salud Carlos III (Grant Numbers PT13/0001/0044, PT17/0009/0019; Instituto Nacional de Bioinformática, INB) and ELIXIR Implementation Studies. The study was further funded by the Federal Ministry of Education and Research, Germany, through the TreatHSP network (01GM1905 to RS and LS), the National Institute of Neurological Diseases and Stroke (R01NS072248 to SZ and RS), the European Joint Program on Rare Diseases-EJP-RD COFUND-EJP N° 825575 through funding for the PROSPAX consortium (441409627 to MS, RS and BvW). CW was supported by the PATE program of the Medical Faculty, University of Tübingen. CEE received support from the Dutch Princess Beatrix Muscle Fund and the Dutch Spieren voor Spieren Muscle fund. Authors on this paper are members of the European Reference Network for Rare Neurological Diseases (ERN-RND, Project ID 739510)
dc.format.mimetype application/pdf
dc.identifier.citation Schüle R, Timmann D, Erasmus CE, Reichbauer J, Wayand M, Solve-RD-DITF-RND et al.Solving unsolved rare neurological diseases-a Solve-RD viewpoint. Eur J Hum Genet. 2021;29:1332-6. DOI: 10.1038/s41431-021-00901-1
dc.identifier.doi http://dx.doi.org/10.1038/s41431-021-00901-1
dc.identifier.issn 1018-4813
dc.identifier.uri http://hdl.handle.net/10230/48024
dc.language.iso eng
dc.publisher Springer Nature
dc.relation.ispartof European Journal of Human Genetics. 2021;29:1332-6
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/779257
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/825575
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/305444
dc.relation.uri https://creativecommons.org/licenses/by/4.0/
dc.rights © Rebecca Schüle et al 2021. This article is licensed under a Creative CommonsAttribution 4.0 International License, which permits use, sharing,adaptation, distribution and reproduction in any medium or format, aslong as you give appropriate credit to the original author(s) and thesource, provide a link to the Creative Commons license, and indicate ifchanges were made
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.subject.other Sistema nerviós -- Malalties
dc.subject.other Malalties rares
dc.title Solving unsolved rare neurological diseases-a Solve-RD viewpoint
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

Col·leccions

Articles (Center for Genomic Regulation (CRG))
Articles (Departament de Medicina i Ciències de la Vida)
Documents OpenAIRE (Open Access Infrastructure for Research in Europe)