PuSH - Publication Server of Helmholtz Zentrum München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Snijders Blok, L.* ; Rousseau, J.* ; Twist, J.* ; Ehresmann, S.* ; Takaku, M.* ; Venselaar, H.* ; Rodan, L.H.* ; Nowak, C.B.* ; Douglas, J.* ; Swoboda, K.J.* ; Steeves, M.A.* ; Sahai, I.* ; Stumpel, C.T.R.M.* ; Stegmann, A.P.A.* ; Wheeler, P.* ; Willing, M.C.* ; Fiala, E.* ; Kochhar, A.* ; Gibson, W.T.* ; Cohen, A.S.A.* ; Agbahovbe, R.* ; Innes, A.M.* ; Au, P.Y.B.* ; Rankin, J.* ; Anderson, I.J.* ; Skinner, S.A.* ; Louie, R.J.* ; Warren, H.E.* ; Afenjar, A.* ; Keren, B.* ; Nava, C.* ; Buratti, J.* ; Isapof, A.* ; Rodriguez, D.* ; Lewandowski, R.* ; Propst, J.* ; van Essen, T.* ; Choi, M.* ; Lee, S.* ; Chae, J.H.* ; Price, S.* ; Schnur, R.E.* ; Douglas, G.* ; Wentzensen, I.M.* ; Zweier, C.* ; Reis, A.* ; Bialer, M.G.* ; Moore, C.* ; Koopmans, M.* ; Brilstra, E.H.* ; Monroe, G.R.* ; van Gassen, K.L.I.* ; van Binsbergen, E.* ; Newbury-Ecob, R.* ; Bownass, L.* ; Bader, I.* ; Mayr, J.A.* ; Wortmann, S.B. ; Jakielski, K.J.* ; Strand, E.A.* ; Kloth, K.* ; Bierhals, T.* ; Roberts, J.D.* ; Petrovich, R.M.* ; Machida, S.* ; Kurumizaka, H.* ; Lelieveld, S.* ; Pfundt, R.* ; Jansen, S.* ; Deriziotis, P.* ; Faive, L.* ; Thevenon, J.* ; Assoum, M.* ; Shriberg, L.* ; Kleefstra, T.* ; Brunner, H.G.* ; Wade, P.A.* ; Fisher, S.E.* ; Campeau, P.M.*

CHD3 helicase domain mutations cause a neurodevelopmental syndrome with macrocephaly and impaired speech and language.

Nat. Commun. 9:4619 (2018)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Chromatin remodeling is of crucial importance during brain development. Pathogenic alterations of several chromatin remodeling ATPases have been implicated in neurodevelopmental disorders. We describe an index case with a de novo missense mutation in CHD3, identified during whole genome sequencing of a cohort of children with rare speech disorders. To gain a comprehensive view of features associated with disruption of this gene, we use a genotype-driven approach, collecting and characterizing 35 individuals with de novo CHD3 mutations and overlapping phenotypes. Most mutations cluster within the ATPase/helicase domain of the encoded protein. Modeling their impact on the three-dimensional structure demonstrates disturbance of critical binding and interaction motifs. Experimental assays with six of the identified mutations show that a subset directly affects ATPase activity, and all but one yield alterations in chromatin remodeling. We implicate de novo CHD3 mutations in a syndrome characterized by intellectual disability, macrocephaly, and impaired speech and language.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
12.353
2.912
36
43
Tags
Annotations
Special Publikation
Hide on homepage

Edit extra information
Edit own tags
Private
Edit own annotation
Private
Hide on publication lists
on hompage
Mark as special
publikation
Publication type Article: Journal article
Document type Scientific Article
Keywords De-novo Mutations; Chromatin Remodeling Complex; Intellectual Disability; Deacetylase Complex; Exome; Disorder; Family; Gene; Nurd; Diagnosis
Language english
Publication Year 2018
HGF-reported in Year 2018
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 9, Issue: 1, Pages: , Article Number: 4619 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)
POF-Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-500700-001
DOI 10.1038/s41467-018-06014-6
WOS ID WOS:000449269900001
Scopus ID 85056256118
PubMed ID 30397230
Erfassungsdatum 2018-11-28
[➜Report correction]