The NuRD complex and macrocephaly associated neurodevelopmental disorders

Tyler Mark Pierson, Maria G. Otero, Katheryn Grand, Andrew Choi, John M. Graham, Juan I. Young, Joel P. Mackay

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


The nucleosome remodeling and deacetylase (NuRD) complex is a major regulator of gene expression involved in pluripotency, lineage commitment, and corticogenesis. This important complex is composed of seven different proteins, with mutations in CHD3, CHD4, and GATAD2B being associated with neurodevelopmental disorders presenting with macrocephaly and intellectual disability similar to other overgrowth and intellectual disability (OGID) syndromes. Pathogenic variants in CHD3 and CHD4 primarily involve disruption of enzymatic function. GATAD2B variants include loss-of-function mutations that alter protein dosage and missense variants that involve either of two conserved domains (CR1 and CR2) known to interact with other NuRD proteins. In addition to macrocephaly and intellectual disability, CHD3 variants are associated with inguinal hernias and apraxia of speech; whereas CHD4 variants are associated with skeletal anomalies, deafness, and cardiac defects. GATAD2B-associated neurodevelopmental disorder (GAND) has phenotypic overlap with both of these disorders. Of note, structural models of NuRD indicate that CHD3 and CHD4 require direct contact with the GATAD2B-CR2 domain to interact with the rest of the complex. Therefore, the phenotypic overlaps of CHD3- and CHD4-related disorders with GAND are consistent with a loss in the ability of GATAD2B to recruit CHD3 or CHD4 to the complex. The shared features of these neurodevelopmental disorders may represent a new class of OGID syndrome: the NuRDopathies.

Original languageEnglish (US)
Pages (from-to)548-556
Number of pages9
JournalAmerican Journal of Medical Genetics, Part C: Seminars in Medical Genetics
Issue number4
StatePublished - Dec 1 2019


  • CHD3
  • CHD4
  • NuRD complex
  • macrocephaly

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'The NuRD complex and macrocephaly associated neurodevelopmental disorders'. Together they form a unique fingerprint.

Cite this