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Updated: Feb 19, 2026
Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
Clinical and molecular effects of CHD7 in the heart
Nicole Corsten-Janssen1, Peter J Scambler2
1Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Insights
Loss-of-function mutations in CHD7 cause heart defects in CHARGE syndrome. Mouse models show CHD7 is crucial for heart development, particularly great vessel formation and septation.
Area of Science:
- Developmental Biology
- Genetics
- Cardiology
Background:
- Loss-of-function mutations in CHD7 are a primary cause of CHARGE syndrome.
- Cardiovascular anomalies are a significant source of morbidity and mortality in CHARGE syndrome patients.
Purpose of the Study:
- To review the clinical and molecular aspects of CHD7 related to cardiovascular manifestations in CHARGE syndrome.
- To elucidate the role of CHD7 in heart development using mouse models.
Main Methods:
- Review of clinical data and molecular studies on CHD7 mutations.
- Analysis of Chd7 haploinsufficiency in mouse models to study heart development.
Main Results:
- Patients with CHD7 mutations exhibit variable heart defects, notably atrioventricular septal defects and outflow tract defects.
- Mouse models demonstrate Chd7's essential role in multiple cell lineages during heart development, including pharyngeal ectoderm and cardiogenic mesoderm.
- Chd7 is required for great vessel formation, atrioventricular cushion development, and outflow tract septation.
Conclusions:
- CHD7 plays a critical, non-autonomous role in the development of the great vessels and septation of the heart.
- CHD7 likely functions in conjunction with transcription factors like TBX1 and SMADs, regulating key cardiac genes.
Abstract:
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.
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