| 1 |
CHD3 helicase domain mutations cause a neurodevelopmental syndrome with macrocephaly and impaired speech and language
|
|
Snijders Blok, Lot; Rousseau, Justine; Twist, Joanna; Ehresmann, Sophie; Takaku, Motoki; Venselaar, Hanka; Rodan, Lance,; Nowak, Catherine,; Douglas, Jessica; Swoboda, Kathryn,; Steeves, Marcie,; Sahai, Inderneel; Stumpel, Connie; Stegmann, Alexander; Wheeler, Patricia; Willing, Marcia; Fiala, Elise; Kochhar, Aaina; Gibson, William,; Cohen, Ana,; Agbahovbe, Ruky; Innes, A. Micheil; Au, P.,; Rankin, Julia; Anderson, Ilse,; Skinner, Steven,; Louie, Raymond,; Warren, Hannah,; Afenjar, Alexandra; Keren, Boris; Nava, Caroline; Buratti, Julien; Isapof, Arnaud; Rodriguez, Diana; Lewandowski, Raymond; Propst, Jennifer; Van Essen, Ton; Choi, Murim; Lee, Sangmoon; Chae, Jong,; Price, Susan; Schnur, Rhonda,; Douglas, Ganka; Wentzensen, Ingrid,; Zweier, Christiane; Reis, André; Bialer, Martin,; Moore, Christine; Koopmans, Marije; Brilstra, Eva; Monroe, Glen,; van Gassen, Koen,; Van Binsbergen, Ellen; Newbury-Ecob, Ruth; Bownass, Lucy; Bader, Ingrid; Mayr, Johannes,; Wortmann, Saskia; Jakielski, Kathy,; Strand, Edythe,; Kloth, Katja; Bierhals, Tatjana; Roberts, John,; Petrovich, Robert,; Machida, Shinichi; Kurumizaka, Hitoshi; Lelieveld, Stefan; Pfundt, Rolph; Jansen, Sandra; Deriziotis, Pelagia; Faive, Laurence; Thevenon, Julien; Assoum, Mirna; Shriberg, Lawrence; Kleefstra, Tjitske; Brunner, Han,; Wade, Paul,; Fisher, Simon; Campeau, Philippe
|
|
In: ISSN: 2041-1723 ; EISSN: 2041-1723 ; Nature Communications ; https://hal.sorbonne-universite.fr/hal-01922858 ; Nature Communications, Nature Publishing Group, 2018, 9 (1), pp.4619. ⟨10.1038/s41467-018-06014-6⟩ (2018)
|
|
Abstract:
International audience ; 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.
|
|
Keyword:
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry; [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis; [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics; [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology; Molecular Biology/Structural Biology [q-bio.BM]
|
|
URL: https://hal.sorbonne-universite.fr/hal-01922858
https://doi.org/10.1038/s41467-018-06014-6
https://hal.sorbonne-universite.fr/hal-01922858/document
https://hal.sorbonne-universite.fr/hal-01922858/file/s41467-018-06014-6.pdf
|
|
BASE
|
|
Hide details
|
|
|
| 2 |
Further delineation of the MECP2 duplication syndrome phenotype in 59 French male patients, with a particular focus on morphological and neurological features
|
|
|
|
In: ISSN: 0022-2593 ; EISSN: 1468-6244 ; Journal of Medical Genetics ; https://hal-univ-bourgogne.archives-ouvertes.fr/hal-02064139 ; Journal of Medical Genetics, BMJ Publishing Group, 2018, 55 (6), pp.jmedgenet-2017-104956. ⟨10.1136/jmedgenet-2017-104956⟩ ; https://jmg.bmj.com/content/55/6/359.long (2018)
|
|
BASE
|
|
Show details
|
|
|
| 3 |
Heterozygous deletion of the LRFN2 gene is associated with working memory deficits
|
|
|
|
In: ISSN: 1018-4813 ; EISSN: 1476-5438 ; European Journal of Human Genetics ; https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01405814 ; European Journal of Human Genetics, Nature Publishing Group, 2016, 24 (6), pp.911 - 918. ⟨10.1038/ejhg.2015.221⟩ ; http://www.nature.com/ejhg/journal/v24/n6/full/ejhg2015221a.html (2016)
|
|
BASE
|
|
Show details
|
|
|
| 4 |
BCL11A Haploinsufficiency Causes an Intellectual Disability Syndrome and Dysregulates Transcription
|
|
|
|
In: ISSN: 0002-9297 ; EISSN: 1537-6605 ; American Journal of Human Genetics ; https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01680178 ; American Journal of Human Genetics, Elsevier (Cell Press), 2016, 99 (2), pp.253 - 274. ⟨10.1016/j.ajhg.2016.05.030⟩ (2016)
|
|
BASE
|
|
Show details
|
|
|
| 5 |
12p13.33 microdeletion including ELKS/ERC1, a new locus associated with childhood apraxia of speech
|
|
|
|
BASE
|
|
Show details
|
|
|
|
|
