Pediatric Cardiology

, Volume 40, Issue 1, pp 17–22 | Cite as

Search of Somatic Mutations of NKX2-5 and GATA4 Genes in Chinese Patients with Sporadic Congenital Heart Disease

  • Jie Yin
  • Jianhua Qian
  • Genyin Dai
  • Chunli Wang
  • Yuming Qin
  • Ting Xu
  • Zewei Li
  • Han Zhang
  • Shiwei YangEmail author
Original Article


Congenital heart disease (CHD) usually occurs sporadically, with only a minority of cases associated with a known genetic mechanism. Cardiac-specific transcription factors NKX2-5 and GATA4 play key roles in the mammalian heart development, and the affected cardiac tissues of CHD patients are prone to somatic mutations which thus participate in the pathogenesis of CHD. We collected 98 patients with sporadic CHD, extracted genomic DNA from cardiac tissues and blood, and then screened NKX2-5 and GATA4 genes using PCR-direct sequence analysis. A novel heterozygous missense mutation (c.907G > A, p.V303I) of NKX2-5 gene was identified in a patient with tetralogy of Fallots. Functional assay revealed that this mutant was associated with significantly reduced transcriptional activity. In addition, we found two known single-nucleotide polymorphisms (SNPs) (rs2277923, rs3729753) in NKX2-5 and two known SNPs (rs56166237, rs3729856) in GATA4. All variations identified in cardiac tissues were consistent with those of peripheral blood, and no somatic mutations were found in cardiac tissues. Our study shows no evidence of NKX2-5 and GATA4 somatic mutations playing a role in the pathogenesis of sporadic CHD.


Congenital heart disease Genetics Transcription factor Somatic mutation Reporter gene analysis 



Congenital heart disease


Tetralogy of Fallots


Atrial septal defects


Ventricular septal defects


Total anomalous pulmonary venous connection


Stenosis of right ventricular outflow tract


Double-chambered right ventricle


Transposition of the great arteries


Double outlet of right ventricle


Right ventricular outflow tract


Single-nucleotide polymorphism.



We thank all the patients and families who participated in this study. We would like to thank all the cardiothoracic surgeons from Nanjing Children’s Hospital for their support regarding CHD heart tissues, and all the doctors of clinical laboratory.


This study was funded by the National Natural Science Foundation of China (Grant Nos. 81670284, 81000076), Nanjing Science and Technology Project (Grant No. 201715057), and Nanjing Medical Science and Technique Development Foundation.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of CardiologyChildren’s Hospital of Nanjing Medical UniversityNanjingChina
  2. 2.Jiangsu Key Laboratory of PediatricsNanjing Medical UniversityNanjingChina
  3. 3.Nanjing Key Laboratory of Pediatrics, Nanjing Children’s HospitalAffiliated to Nanjing Medical UniversityNanjingChina

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