An update on the molecular diagnosis of congenital heart disease: focus on loss-of-function mutations

Expert Rev Mol Diagn. 2017 Apr;17(4):393-401. doi: 10.1080/14737159.2017.1300062. Epub 2017 Mar 8.


Congenital heart disease (CHD) is the most common birth defect in humans. In spite of tremendous advance in medical care, CHD is still a major contributor to substantial morbidity and mortality. Aggregating evidence demonstrates that genetic defects play a pivotal role in the pathogenesis of CHD, and an increasing number of genetic mutations have been identified to be responsible for CHD. Areas covered: This paper is restricted to the molecular diagnosis of CHD, and highlights loss-of-function mutations in the genes associated with CHD. The newly-made progress in the molecular genetics of CHD is reviewed in this article. Expert commentary: Heart development is a precisely-coordinated biological process, involving in cellular proliferation, differentiation, migration, and integrated morphogenetic interactions, and interruption of this process predominantly by genetic risk factors leads to CHD. To date, mutations in over 60 genes have been causally linked to CHD, of which most mutations cause a loss-of-function effect. Using next generation sequencing technology and data processing software, new CHD-associated genes will be more easily discovered. Identification of the CHD-causative genes is of significant importance in genetic diagnosis, early prophylaxis and personalized treatment of CHD patients.

Keywords: Congenital heart disease; gene mutation; genetic testing; loss of function; molecular genetics.

Publication types

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

MeSH terms

  • Heart Defects, Congenital / diagnosis*
  • Heart Defects, Congenital / genetics*
  • Humans
  • Molecular Diagnostic Techniques / methods*
  • Molecular Diagnostic Techniques / trends
  • Mutation*