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

Lot Snijders Blok, Justine Rousseau, Joanna Twist, Sophie Ehresmann, Motoki Takaku, Hanka Venselaar, Lance H. Rodan, Catherine B. Nowak, Jessica Douglas, Kathryn J. Swoboda, Marcie A. Steeves, Inderneel Sahai, Connie T. R. M. Stumpel, Alexander P. A. Stegmann, Patricia Wheeler, Marcia Willing, Elise Fiala, Aaina Kochhar, William T. Gibson, Ana S. A. Cohen, Ruky Agbahovbe, A. Micheil Innes, P. Y. Billie Au, Julia Rankin, Ilse J. Anderson, Steven A. Skinner, Raymond J. Louie, Hannah E. Warren, Alexandra Afenjar, Boris Keren, Caroline Nava, Julien Buratti, Arnaud Isapof, Diana Rodriguez, Raymond Lewandowski, Jennifer Propst, Ton van Essen, Murim Choi, Sangmoon Lee, Jong H. Chae, Susan Price, Rhonda E. Schnur, Ganka Douglas, Ingrid M. Wentzensen, Christiane Zweier, André Reis, Martin G. Bialer, Christine Moore, Marije Koopmans, Eva H. Brilstra, Glen R. Monroe, Koen L. I. van Gassen, Ellen van Binsbergen, Ruth Newbury-Ecob, Lucy Bownass, Ingrid Bader, Johannes A. Mayr, Saskia B. Wortmann, Kathy J. Jakielski, Edythe A. Strand, Katja Kloth, Tatjana Bierhals, John D. Roberts, Robert M. Petrovich, Shinichi Machida, Hitoshi Kurumizaka, Stefan Lelieveld, Rolph Pfundt, Sandra Jansen, Pelagia Deriziotis, Laurence Faive, Julien Thevenon, Mirna Assoum, Lawrence Shriberg, Tjitske Kleefstra, Han G. Brunner, Paul A. Wade, Simon E. Fisher, Philippe M. Campeau
  • Nature Communications, November 2018, Springer Science + Business Media
  • DOI: 10.1038/s41467-018-06014-6

Mutations in the gene CHD3 can cause a language disorder with cognitive delays and a larger head.

What is it about?

We studied individuals with mutations in CHD3. They tended to have a delayed development, especially their language development, and later on various degrees of intellectual disability. Some characteristics were in common between many individuals, such as a larger head, a flat facial profile, eyes more set apart, joint laxity and hernias. We studied the effect of the mutations in vitro. Several decreased the ability of CHD3 to remodel nucleosomes, while others had no in vitro effect or in fact increased the activity.

Why is it important?

We defined the clinical characteristics of individuals with dysfunctional CHD3, thus allowing us to better know this genetic condition, and also allowing us to start to understand what happens in the cells and eventually in the neurons of such individuals.


Dr Philippe M Campeau
Universite de Montreal

We will now try to understand what are the consequences of this CHD3 dysregulation on gene expression and regulation in neurons, and we will continue expanding the phenotypic spectrum of this condition.

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The following have contributed to this page: Dr Philippe M Campeau