Clinical and molecular effects of CHD7 in the heart

Am J Med Genet C Semin Med Genet. 2017 Dec;175(4):487-495. doi: 10.1002/ajmg.c.31590. Epub 2017 Oct 31.


Heart defects caused by loss-of-function mutations in CHD7 are a frequent cause of morbidity and mortality in CHARGE syndrome. Here we review the clinical and molecular aspects of CHD7 that are related to the cardiovascular manifestations of the syndrome. The types of heart defects found in patients with CHD7 mutations are variable, with an overrepresentation of atrioventricular septal defect and outflow tract defect including aortic arch anomalies compared to nonsyndromic heart defects. Chd7 haploinsufficiency in mouse is a good model for studying the heart effects seen in CHARGE syndrome, and mouse models reveal a role for Chd7 in multiple lineages during heart development. Formation of the great vessels requires Chd7 expression in the pharyngeal surface ectoderm, and this expression likely has an non-autonomous effect on neural crest cells. In the cardiogenic mesoderm, Chd7 is required for atrioventricular cushion development and septation of the outflow tract. Emerging knowledge about the function of CHD7 in the heart indicates that it may act in concert with transcription factors such as TBX1 and SMADs to regulate genes such as p53 and the cardiac transcription factor NKX2.5.

Keywords: CHARGE syndrome; CHD7; congenital heart defects.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Proteins / metabolism
  • CHARGE Syndrome / diagnosis
  • CHARGE Syndrome / genetics
  • DNA Helicases / genetics*
  • DNA Helicases / metabolism
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Disease Models, Animal
  • Genetic Association Studies*
  • Heart Defects, Congenital / diagnosis*
  • Heart Defects, Congenital / genetics*
  • Humans
  • Mice
  • Mutation*
  • Organ Specificity / genetics
  • Organogenesis / genetics
  • Phenotype*
  • Signal Transduction


  • Bone Morphogenetic Proteins
  • DNA-Binding Proteins
  • DNA Helicases
  • CHD7 protein, human