Abstract

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.

Details

Title
CHD3 helicase domain mutations cause a neurodevelopmental syndrome with macrocephaly and impaired speech and language
Author
Lot Snijders Blok 1   VIAFID ORCID Logo  ; Rousseau, Justine 2 ; Twist, Joanna 3 ; Ehresmann, Sophie 2 ; Takaku, Motoki 3 ; Venselaar, Hanka 4 ; Rodan, Lance H 5 ; Nowak, Catherine B 5 ; Douglas, Jessica 5 ; Swoboda, Kathryn J 6 ; Steeves, Marcie A 7 ; Sahai, Inderneel 7 ; Connie T R M Stumpel 8 ; Stegmann, Alexander P A 8 ; Wheeler, Patricia 9 ; Willing, Marcia 10 ; Fiala, Elise 10 ; Kochhar, Aaina 11 ; Gibson, William T 12 ; Cohen, Ana S A 12   VIAFID ORCID Logo  ; Agbahovbe, Ruky 12 ; Innes, A Micheil 13   VIAFID ORCID Logo  ; Au, P Y Billie 13 ; Rankin, Julia 14 ; Anderson, Ilse J 15 ; Skinner, Steven A 16 ; Louie, Raymond J 16 ; Warren, Hannah E 16 ; Afenjar, Alexandra 17 ; Keren, Boris 18 ; Nava, Caroline 19 ; Buratti, Julien 20 ; Isapof, Arnaud 21 ; Rodriguez, Diana 22 ; Lewandowski, Raymond 23 ; Propst, Jennifer 23 ; Ton van Essen 24 ; Choi, Murim 25 ; Lee, Sangmoon 25 ; Chae, Jong H 26 ; Price, Susan 27 ; Schnur, Rhonda E 28 ; Ganka Douglas 28 ; Wentzensen, Ingrid M 28 ; Zweier, Christiane 29 ; Reis, André 29 ; Bialer, Martin G 30 ; Moore, Christine 30 ; Koopmans, Marije 31 ; Brilstra, Eva H 31 ; Monroe, Glen R 31 ; Koen L I van Gassen 31 ; Ellen van Binsbergen 31 ; Newbury-Ecob, Ruth 32 ; Bownass, Lucy 32 ; Bader, Ingrid 33 ; Mayr, Johannes A 34 ; Wortmann, Saskia B 35 ; Jakielski, Kathy J 36 ; Strand, Edythe A 37 ; Kloth, Katja 38 ; Bierhals, Tatjana 38 ; McRae, Jeremy F 39 ; Clayton, Stephen 39 ; Fitzgerald, Tomas W 39 ; Kaplanis, Joanna 39 ; Prigmore, Elena 39 ; Rajan, Diana 39 ; Sifrim, Alejandro 39 ; Aitken, Stuart 40 ; Akawi, Nadia 39 ; Alvi, Mohsan 41 ; Ambridge, Kirsty 39 ; Barrett, Daniel M 39 ; Bayzetinova, Tanya 39 ; Jones, Philip 39 ; Jones, Wendy D 39 ; King, Daniel 39 ; Krishnappa, Netravathi 39 ; Mason, Laura E 39 ; Singh, Tarjinder 39 ; Tivey, Adrian R 39 ; Munaza Ahmed 42 ; Uruj Anjum 43 ; Archer, Hayley 44 ; Armstrong, Ruth 45 ; Awada, Jana 39 ; Balasubramanian, Meena 46 ; Banka, Siddharth 47 ; Baralle, Diana 42 ; Barnicoat, Angela 48 ; Batstone, Paul 49 ; Baty, David 50 ; Bennett, Chris 51 ; Berg, Jonathan 50 ; Bernhard, Birgitta 52 ; Bevan, A Paul 39 ; Bitner-Glindzicz, Maria 48 ; Blair, Edward 53 ; Blyth, Moira 51 ; Bohanna, David 54 ; Bourdon, Louise 52 ; Bourn, David 55 ; Bradley, Lisa 56 ; Brady, Angela 52 ; Simon, Brent 39 ; Brewer, Carole 57 ; Brunstrom, Kate 48 ; Bunyan, David J 42 ; Burn, John 55 ; Canham, Natalie 52 ; Castle, Bruce 57 ; Chandler, Kate 47 ; Chatzimichali, Elena 39 ; Cilliers, Deirdre 53 ; Clarke, Angus 44 ; Clasper, Susan 53 ; Clayton-Smith, Jill 47 ; Clowes, Virginia 52 ; Coates, Andrea 51 ; Cole, Trevor 54 ; Colgiu, Irina 39 ; Collins, Amanda 42 ; Collinson, Morag N 42 ; Connell, Fiona 58 ; Cooper, Nicola 54 ; Cox, Helen 54 ; Cresswell, Lara 59 ; Cross, Gareth 60 ; Crow, Yanick 47 ; Mariella D’Alessandro 49 ; Tabib Dabir 56 ; Davidson, Rosemarie 61 ; Davies, Sally 44 ; de Vries, Dylan 39 ; Dean, John 49 ; Deshpande, Charu 58 ; Devlin, Gemma 57 ; Dixit, Abhijit 60 ; Dobbie, Angus 51 ; Donaldson, Alan 62 ; Donnai, Dian 47 ; Donnelly, Deirdre 56 ; Donnelly, Carina 47 ; Douglas, Angela 63 ; Douzgou, Sofia 47 ; Duncan, Alexis 61 ; Eason, Jacqueline 60 ; Ellard, Sian 57 ; Ellis, Ian 63 ; Elmslie, Frances 43 ; Evans, Karenza 44 ; Everest, Sarah 57 ; Fendick, Tina 58 ; Fisher, Richard 55 ; Flinter, Frances 58 ; Foulds, Nicola 42 ; Fry, Andrew 44 ; Fryer, Alan 63 ; Gardiner, Carol 61 ; Gaunt, Lorraine 47 ; Ghali, Neeti 52 ; Gibbons, Richard 53 ; Gill, Harinder 64 ; Goodship, Judith 55 ; Goudie, David 50 ; Gray, Emma 39 ; Green, Andrew 64 ; Greene, Philip 39 ; Greenhalgh, Lynn 63 ; Gribble, Susan 39 ; Harrison, Rachel 60 ; Harrison, Lucy 42 ; Harrison, Victoria 42 ; Hawkins, Rose 62 ; Liu, He 39 ; Hellens, Stephen 55 ; Henderson, Alex 55 ; Hewitt, Sarah 51 ; Hildyard, Lucy 39 ; Hobson, Emma 51 ; Holden, Simon 45 ; Holder, Muriel 52 ; Holder, Susan 52 ; Hollingsworth, Georgina 48 ; Homfray, Tessa 43 ; Humphreys, Mervyn 56 ; Hurst, Jane 48 ; Hutton, Ben 39 ; Ingram, Stuart 46 ; Irving, Melita 58 ; Islam, Lily 54 ; Jackson, Andrew 40 ; Jarvis, Joanna 54 ; Jenkins, Lucy 48 ; Johnson, Diana 46 ; Jones, Elizabeth 47 ; Josifova, Dragana 58 ; Joss, Shelagh 61 ; Kaemba, Beckie 59 ; Kazembe, Sandra 59 ; Kelsell, Rosemary 39 ; Kerr, Bronwyn 47 ; Kingston, Helen 47 ; Kini, Usha 53 ; Kinning, Esther 61 ; Kirby, Gail 54 ; Kirk, Claire 56 ; Kivuva, Emma 57 ; Kraus, Alison 51 ; Kumar, Dhavendra 44 ; Ajith Kumar, V K 48 ; Lachlan, Katherine 42 ; Lam, Wayne 40 ; Lampe, Anne 40 ; Langman, Caroline 58 ; Lees, Melissa 48 ; Lim, Derek 54 ; Longman, Cheryl 61 ; Lowther, Gordon 61 ; Lynch, Sally A 64 ; Magee, Alex 56 ; Maher, Eddy 40 ; Male, Alison 48 ; Mansour, Sahar 43 ; Marks, Karen 43 ; Martin, Katherine 60 ; Maye, Una 63 ; McCann, Emma 65 ; McConnell, Vivienne 56 ; McEntagart, Meriel 43 ; McGowan, Ruth 49 ; McKay, Kirsten 54 ; McKee, Shane 56 ; McMullan, Dominic J 54 ; McNerlan, Susan 56 ; McWilliam, Catherine 49 ; Mehta, Sarju 45 ; Metcalfe, Kay 47 ; Middleton, Anna 39 ; Miedzybrodzka, Zosia 49 ; Miles, Emma 47 ; Mohammed, Shehla 58 ; Montgomery, Tara 55 ; Moore, David 40 ; Morgan, Sian 44 ; Morton, Jenny 54 ; Hood Mugalaasi 44 ; Murday, Victoria 61 ; Murphy, Helen 47 ; Naik, Swati 54 ; Nemeth, Andrea 53 ; Nevitt, Louise 46 ; Norman, Andrew 54 ; Rosie O’Shea 64 ; Ogilvie, Caroline 58 ; Kai-Ren Ong 54 ; Park, Soo-Mi 45 ; Parker, Michael J 46 ; Patel, Chirag 54 ; Paterson, Joan 45 ; Payne, Stewart 52 ; Perrett, Daniel 39 ; Phipps, Julie 53 ; Pilz, Daniela T 61 ; Pollard, Martin 39 ; Pottinger, Caroline 65 ; Poulton, Joanna 53 ; Pratt, Norman 50 ; Prescott, Katrina 51 ; Pridham, Abigail 53 ; Procter, Annie 44 ; Purnell, Hellen 53 ; Quarrell, Oliver 46 ; Ragge, Nicola 54 ; Rahbari, Raheleh 39 ; Randall, Josh 39 ; Raymond, Lucy 45 ; Rice, Debbie 50 ; Leema, Robert 58 ; Roberts, Eileen 62 ; Roberts, Jonathan 45 ; Roberts, Paul 51 ; Roberts, Gillian 63 ; Ross, Alison 49 ; Rosser, Elisabeth 48 ; Saggar, Anand 43 ; Samant, Shalaka 49 ; Sampson, Julian 44 ; Sandford, Richard 45 ; Sarkar, Ajoy 60 ; Schweiger, Susann 50 ; Scott, Richard 48 ; Scurr, Ingrid 62 ; Selby, Ann 60 ; Seller, Anneke 53 ; Sequeira, Cheryl 52 ; Shannon, Nora 60 ; Sharif, Saba 54 ; Shaw-Smith, Charles 57 ; Shearing, Emma 46 ; Shears, Debbie 53 ; Sheridan, Eamonn 51 ; Simonic, Ingrid 45 ; Roldan Singzon 52 ; Skitt, Zara 47 ; Smith, Audrey 51 ; Smith, Kath 46 ; Smithson, Sarah 62 ; Sneddon, Linda 55 ; Splitt, Miranda 55 ; Squires, Miranda 51 ; Stewart, Fiona 56 ; Stewart, Helen 53 ; Straub, Volker 55 ; Suri, Mohnish 60 ; Sutton, Vivienne 63 ; Ganesh Jawahar Swaminathan 39 ; Sweeney, Elizabeth 63 ; Tatton-Brown, Kate 43 ; Taylor, Cat 3 ; Taylor, Rohan 43 ; Tein, Mark 54 ; Temple, I Karen 42 ; Thomson, Jenny 51 ; Tischkowitz, Marc 45 ; Tomkins, Susan 62 ; Torokwa, Audrey 42 ; Treacy, Becky 45 ; Turner, Claire 57 ; Turnpenny, Peter 57 ; Tysoe, Carolyn 57 ; Vandersteen, Anthony 52 ; Varghese, Vinod 44 ; Vasudevan, Pradeep 59 ; Parthiban Vijayarangakannan 39 ; Vogt, Julie 54 ; Wakeling, Emma 52 ; Wallwark, Sarah 45 ; Waters, Jonathon 48 ; Weber, Astrid 63 ; Wellesley, Diana 42 ; Whiteford, Margo 61 ; Widaa, Sara 39 ; Wilcox, Sarah 45 ; Wilkinson, Emily 39 ; Williams, Denise 54 ; Williams, Nicola 61 ; Wilson, Louise 48 ; Woods, Geoff 45 ; Wragg, Christopher 62 ; Wright, Michael 55 ; Yates, Laura 55 ; Yau, Michael 58 ; Nellåker, Chris 66 ; Parker, Michael 67 ; Firth, Helen V 68 ; Wright, Caroline F 39 ; FitzPatrick, David R 69 ; Barrett, Jeffrey C 39 ; Hurles, Matthew E 39 ; Roberts, John D 3 ; Petrovich, Robert M 3 ; Machida, Shinichi 70 ; Kurumizaka, Hitoshi 70   VIAFID ORCID Logo  ; Lelieveld, Stefan 71 ; Rolph Pfundt 71 ; Jansen, Sandra 72 ; Deriziotis, Pelagia 73 ; Faivre, Laurence 74 ; Thevenon, Julien 74 ; Assoum, Mirna 74 ; Shriberg, Lawrence 75 ; Kleefstra, Tjitske 72 ; Brunner, Han G 76 ; Wade, Paul A 3   VIAFID ORCID Logo  ; Fisher, Simon E 77   VIAFID ORCID Logo  ; Campeau, Philippe M 78   VIAFID ORCID Logo 

1  Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands; Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands; Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands 
2  CHU Sainte-Justine Research Center, Montreal, Canada 
3  National Institute of Environmental Health Sciences, Research Triangle Park, USA 
4  Centre for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands 
5  Division of Genetics and Genomics, Boston Children’s Hospital, Boston, USA 
6  Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, USA 
7  Department of Medical Genetics, Massachusetts General Hospital, Boston, USA 
8  Department of Clinical Genetics and GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands 
9  Nemours Childrens Clinic, Orlando, USA 
10  Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, USA 
11  Valley Children’s Hospital, Madera, USA 
12  British Columbia Children’s Hospital Research Institute, Vancouver, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, Canada 
13  Department of Medical Genetics and Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada 
14  Department of Clinical Genetics, Royal Devon and Exeter NHS Foundation Trust (Heavitree), Exeter, UK 
15  Division of Genetics, Department of Medicine, University of Tennessee Medical Center, Knoxville, USA 
16  Greenwood Genetic Center, Greenwood, USA 
17  GRC ConCer-LD, Sorbonne Universités, UPMC Univ Paris ; Department of Medical Genetics and Centre de Référence Malformations et maladies congénitales du cervelet et déficiences intellectuelles de causes rares, Armand Trousseau Hospital, GHUEP, AP-HP, Paris, France 
18  AP-HP, Hôpital de la Pitié-Salpêtrière, Département de Génétique, Paris, France; Groupe de Recherche Clinique (GRC) ‘déficience intellectuelle et autisme’ UPMC, Paris, France 
19  AP-HP, Hôpital de la Pitié-Salpêtrière, Département de Génétique, Paris, France; Groupe de Recherche Clinique (GRC) ‘déficience intellectuelle et autisme’ UPMC, Paris, France; INSERM, U 1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle épinière, ICM, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Paris, France 
20  AP-HP, Hôpital de la Pitié-Salpêtrière, Département de Génétique, Paris, France 
21  GRC ConCer-LD, Sorbonne Universités, UPMC Univ Paris 06; Department Child Neurology and Reference Center for Neuromuscular Diseases “Nord/Est/Ile-de-France”, FILNEMUS, Armand Trousseau Hospital, GHUEP, AP-HP, Paris, France 
22  GRC ConCer-LD, Sorbonne Universités, UPMC Univ Paris 06; Department of Child Neurology and National Reference Center for Neurogenetic Disorders, Armand Trousseau Hospital, GHUEP, AP-HP, INSERM U1141, Paris, France 
23  Clinical Genetics Division, Virginia Commonwealth University Health System, Richmond, USA 
24  Clinical Genetics Department, University Medical Center Groningen, Groningen, The Netherlands 
25  Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea 
26  Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children’s Hospital, Seoul, Republic of Korea 
27  Oxford University Hospitals NHS Foundation Trust, Oxford, UK 
28  GeneDx, Gaithersburg, USA 
29  Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany 
30  Northwell Health, Division of Medical Genetics and Genomics, Great Neck, USA 
31  Department of Genetics, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands 
32  University Hospitals Bristol, Department of Clinical Genetics, St Michael’s Hospital, Bristol, UK 
33  Department of Clinical Genetics, University Children’s Hospital, Paracelsus Medical University, Salzburg, Austria 
34  Department of Pediatrics, Salzburger Landeskliniken and Paracelsus Medical University, Salzburg, Austria 
35  Department of Pediatrics, Salzburger Landeskliniken and Paracelsus Medical University, Salzburg, Austria; Institute of Human Genetics, Technische Universität München, Munich, Germany; Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany 
36  Communication Sciences and Disorders, Augustana College, Rock Island, USA 
37  Department of Neurology, Mayo Clinic, Rochester, USA 
38  Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 
39  Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK 
40  MRC Human Genetics Unit, MRC IGMM, University of Edinburgh, Western General Hospital, Edinburgh, UK 
41  Department of Engineering Science, University of Oxford, Parks Road, Oxford, UK 
42  Wessex Clinical Genetics Service, University Hospital Southampton, Princess Anne Hospital, Southampton, UK; Wessex Regional Genetics Laboratory, Salisbury NHS Foundation Trust, Salisbury District Hospital, Salisbury, Wiltshire, UK; Faculty of Medicine, University of Southampton, Southampton, UK 
43  South West Thames Regional Genetics Centre, St George’s Healthcare NHS Trust, St George’s, University of London, London, UK 
44  Institute of Medical Genetics, University Hospital of Wales, Cardiff, UK; Department of Clinical Genetics, Block 12, Glan Clwyd Hospital, Rhyl, Denbighshire, UK 
45  East Anglian Medical Genetics Service, Box 134, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK 
46  Sheffield Regional Genetics Services, Sheffield Children’s NHS Trust, Sheffield, UK 
47  Manchester Centre for Genomic Medicine, St Mary’s Hospital, Central Manchester University Hospitals NHSFoundation Trust, Manchester Academic Health Science Centre, Manchester, UK 
48  North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street Hospital, Great Ormond Street, London, UK 
49  North of Scotland Regional Genetics Service, NHS Grampian, Department of Medical Genetics Medical School, Aberdeen, UK 
50  East of Scotland Regional Genetics Service, Human Genetics Unit, Pathology Department, NHS Tayside, Ninewells Hospital, Dundee, UK 
51  Yorkshire Regional Genetics Service, Leeds Teaching Hospitals NHS Trust, Department of Clinical Genetics, Chapel Allerton Hospital, Leeds, UK 
52  North West Thames Regional Genetics Centre, North West London Hospitals NHS Trust, The Kennedy Galton Centre, Northwick Park and St Mark’s NHS Trust Watford Road, Harrow, UK 
53  Oxford Regional Genetics Service, Oxford Radcliffe Hospitals NHS Trust, Oxford, UK 
54  West Midlands Regional Genetics Service, Birmingham Women’s NHS Foundation Trust, Birmingham Women’s Hospital, Edgbaston, Birmingham, UK 
55  Northern Genetics Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Institute of Human Genetics, International Centre for Life, Newcastle upon Tyne, UK 
56  Northern Ireland Regional Genetics Centre, Belfast Health and Social Care Trust, Belfast City Hospital, Belfast, UK 
57  Peninsula Clinical Genetics Service, Royal Devon and Exeter NHS Foundation Trust, Clinical Genetics Department, Royal Devon & Exeter Hospital (Heavitree), Exeter, UK 
58  South East Thames Regional Genetics Centre, Guy’s and St Thomas’ NHS Foundation Trust, Guy’s Hospital, London, UK 
59  Leicestershire Genetics Centre, University Hospitals of Leicester NHS Trust, Leicester Royal Infirmary (NHS Trust), Leicester, UK 
60  Nottingham Regional Genetics Service, City Hospital Campus, Nottingham University Hospitals NHS Trust, The Gables, Nottingham, UK 
61  West of Scotland Regional Genetics Service, NHS Greater Glasgow and Clyde, Institute of Medical Genetics, Yorkhill Hospital, Glasgow, UK 
62  Bristol Genetics Service (Avon, Somerset, Gloucs and West Wilts), University Hospitals Bristol NHS Foundation Trust,  St Michael’s Hospital, St Michael’s Hill, Bristol, UK 
63  Merseyside and Cheshire Genetics Service, Liverpool Women’s NHS Foundation Trust, Department of Clinical Genetics, Royal Liverpool Children’s Hospital Alder Hey, Liverpool, UK 
64  National Centre for Medical Genetics, Our Lady’s Children’s Hospital, Crumlin, Dublin 12, Ireland 
65  Department of Clinical Genetics, Block 12, Glan Clwyd Hospital, Rhyl, Denbighshire, Wales, UK 
66  Nuffield Department of Obstetrics & Gynaecology, University of Oxford, Level 3, Women’s Centre, John Radcliffe Hospital, Oxford, UK; Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, UK; Big Data Institute, University of Oxford, Oxford, UK 
67  The Ethox Centre, Nuffield Department of Population Health, University of Oxford, Oxford, UK 
68  Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK; East Anglian Medical Genetics Service, Box 134, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK 
69  Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK; MRC Human Genetics Unit, MRC IGMM, University of Edinburgh, Western General Hospital, Edinburgh, UK 
70  Waseda University, Tokyo, Japan 
71  Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands 
72  Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands; Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands 
73  Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands 
74  Equipe Génétique des Anomalies du Développement, Université de Bourgogne-Franche Comté, Dijon, France; Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs, FHU TRANSLAD, Hôpital d’Enfants, CHU Dijon et Université de Bourgogne, Dijon, France 
75  Waisman Center, Phonology Project, Madison, USA 
76  Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands; Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands; Department of Clinical Genetics and GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands 
77  Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands; Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands 
78  CHU Sainte-Justine Research Center, Montreal, Canada; Sainte-Justine Hospital, University of Montreal, Montreal, Canada 
Pages
1-12
Publication year
2018
Publication date
Nov 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-06014-6
ProQuest document ID
2130051813
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.