PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Brunet, T.* ; Jech, R.* ; Brugger, M.* ; Kovacs, R.* ; Alhaddad, B.* ; Leszinski, G.* ; Riedhammer, K.M.* ; Westphal, D.S.* ; Mahle, I.* ; Mayerhanser, K.* ; Škorvánek, M.* ; Weber, S. ; Graf, E. ; Berutti, R.* ; Necpál, J.* ; Havránková, P.* ; Pavelekova, P.* ; Hempel, M.* ; Kotzaeridou, U.* ; Hoffmann, G.F.* ; Leiz, S.* ; Makowski, C.* ; Roser, T.* ; Schroeder, S.A.* ; Steinfeld, R.* ; Strobl-Wildemann, G.* ; Hoefele, J.* ; Borggraefe, I.* ; Distelmaier, F.* ; Strom, T.M.* ; Winkelmann, J. ; Meitinger, T.* ; Zech, M. ; Wagner, M.

De novo variants in neurodevelopmental disorders-experiences from a tertiary care center.

Clin. Genet. 100, 14-28 (2021)
Verlagsversion DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
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.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
4.438
0.000
6
18
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Autism ; Candidate Gene ; De Novo Variant ; Exome Sequencing ; Intellectual Disability ; Neurodevelopmental Disorder ; Reanalysis
Sprache englisch
Veröffentlichungsjahr 2021
HGF-Berichtsjahr 2021
ISSN (print) / ISBN 0009-9163
e-ISSN 1399-0004
Zeitschrift Clinical Genetics
Quellenangaben Band: 100, Heft: 1, Seiten: 14-28 Artikelnummer: , Supplement: ,
Verlag Wiley
Verlagsort 111 River St, Hoboken 07030-5774, Nj Usa
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Neurogenomics (ING)
Institute of Human Genetics (IHG)
POF Topic(s) 30205 - Bioengineering and Digital Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-503200-001
G-500700-001
Förderungen Slovak Grant and Development Agency under contract
Operational Programme Integrated Infrastructure
Czech Ministry of Education under grant
Charles University, Prague, Czech Republic
DOI 10.1111/cge.13946
WOS ID WOS:000623501000001
Scopus ID 85101839280
PubMed ID 33619735
Erfassungsdatum 2021-05-10
[➜Korrektur melden]