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De novo variants in neurodevelopmental disorders-experiences from a tertiary care center
T. Brunet, R. Jech, M. Brugger, R. Kovacs, B. Alhaddad, G. Leszinski, KM. Riedhammer, DS. Westphal, I. Mahle, K. Mayerhanser, M. Skorvanek, S. Weber, E. Graf, R. Berutti, J. Necpál, P. Havránková, P. Pavelekova, M. Hempel, U. Kotzaeridou, GF....
Jazyk angličtina Země Dánsko
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
33619735
DOI
10.1111/cge.13946
Knihovny.cz E-zdroje
- MeSH
- centra terciární péče MeSH
- dítě MeSH
- dospělí MeSH
- exom genetika MeSH
- fenotyp MeSH
- genetická predispozice k nemoci genetika MeSH
- genetická variace genetika MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- neurovývojové poruchy genetika MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- retrospektivní studie MeSH
- sekvenování exomu metody MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Up to 40% of neurodevelopmental disorders (NDDs) such as intellectual disability, developmental delay, autism spectrum disorder, and developmental motor abnormalities have a documented underlying monogenic defect, primarily due to de novo variants. Still, the overall burden of de novo variants as well as novel disease genes in NDDs await discovery. We performed parent-offspring trio exome sequencing in 231 individuals with NDDs. Phenotypes were compiled using human phenotype ontology terms. The overall diagnostic yield was 49.8% (n = 115/231) with de novo variants contributing to more than 80% (n = 93/115) of all solved cases. De novo variants affected 72 different-mostly constrained-genes. In addition, we identified putative pathogenic variants in 16 genes not linked to NDDs to date. Reanalysis performed in 80 initially unsolved cases revealed a definitive diagnosis in two additional cases. Our study consolidates the contribution and genetic heterogeneity of de novo variants in NDDs highlighting trio exome sequencing as effective diagnostic tool for NDDs. Besides, we illustrate the potential of a trio-approach for candidate gene discovery and the power of systematic reanalysis of unsolved cases.
Department of Nephrology Klinikum rechts der Isar Technical University of Munich Munich Germany
Department of Neurology P J Safarik University Kosice Slovakia
Department of Neurology University Hospital L Pasteur Kosice Slovakia
Department of Neurology Zvolen Hospital Zvolen Slovakia
Department of Pediatrics Technische Universität München Munich Germany
Division of Pediatric Neurology University Children's Hospital Zurich Zurich Switzerland
Divison of Neuropediatrics Clinic for Children and Adolescents Dritter Orden Munich Germany
Institute of Human Genetics Helmholtz Zentrum München Neuherberg Germany
Institute of Human Genetics University Medical Center Hamburg Eppendorf Hamburg Germany
Institute of Neurogenomics Helmholtz Zentrum München Neuherberg Germany
Munich Cluster for Systems Neurology Munich Germany
Neurogenetics Technische Universität München Munich Germany
Citace poskytuje Crossref.org
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