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Solving unsolved rare neurological diseases-a Solve-RD viewpoint
- Source :
- European Journal of Human Genetics, 29, 1332-1336, European journal of human genetics, European journal of human genetics, 29(9):13321336, European Journal of Human Genetics, 29(9), 1332-1336. Nature Publishing Group, European journal of human genetics 29(9), 1332-1336 (2021). doi:10.1038/s41431-021-00901-1, European Journal of Human Genetics, European Journal of Human Genetics, 29, 9, pp. 1332-1336
- Publication Year :
- 2021
-
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. 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)
- Subjects :
- genetics [Rare Diseases]
lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4]
Medizin
Datasets as Topic
0302 clinical medicine
Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14]
Medicine
Genetics (clinical)
0303 health sciences
methods [Genomics]
Management science
Neurodevelopmental disorders
Neurodegenerative diseases
030305 genetics & heredity
1184 Genetics, developmental biology, physiology
Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6]
Genomics
Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3]
genetics [Nervous System Diseases]
3. Good health
Chemistry
Practice Guidelines as Topic
Malalties rares
pathology [Rare Diseases]
methods [Genetic Testing]
Movement disorders
Other Research Donders Center for Medical Neuroscience [Radboudumc 0]
Socio-culturale
standards [Exome Sequencing]
standards [Genetic Testing]
pathology [Nervous System Diseases]
03 medical and health sciences
Rare Diseases
Viewpoint
Exome Sequencing
Genetics
Humans
Genetic Testing
ddc:610
Biology
Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7]
business.industry
Sistema nerviós -- Malalties
methods [Exome Sequencing]
standards [Genomics]
3111 Biomedicine
Human medicine
Nervous System Diseases
business
Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19]
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 10184813 and 14765438
- Volume :
- 29
- Database :
- OpenAIRE
- Journal :
- European Journal of Human Genetics
- Accession number :
- edsair.doi.dedup.....45e3344adf17454c1199c46a86410df8