Pediatric Cardiology

, Volume 33, Issue 4, pp 539–546

A Novel GATA4 Loss-of-Function Mutation Associated With Congenital Ventricular Septal Defect

  • Yi-Qing Yang
  • Li Li
  • Juan Wang
  • Xing-Yuan Liu
  • Xiao-Zhong Chen
  • Wei Zhang
  • Xiao-Zhou Wang
  • Jin-Qi Jiang
  • Xu Liu
  • Wei-Yi Fang
Original Article


Ventricular septal defect (VSD) is the most prevalent type of congenital heart disease and a major cause for the significantly increased morbidity and mortality among infants. Aggregating evidence indicates that genetic defects are involved in the pathogenesis of congenital VSD. Nevertheless, VSD is genetically heterogeneous, and the genetic determinants for VSD in the majority of patients remain to be identified. In this study, the entire coding region of GATA4, a gene encoding a zinc finger transcription factor essential for normal cardiac morphogenesis, was sequenced in 160 unrelated patients with VSD. The available relatives of the index patient harboring the identified mutation and 200 unrelated control individuals were subsequently genotyped. The disease-causing potential of a sequence alteration was evaluated by MutationTaster, and the functional effect of the mutation was characterized using a luciferase reporter assay system. As a result, a novel heterozygous GATA4 variation, p.R43W, was identified in a proband with VSD, that was absent in control subjects. Genetic analysis of the family members of the variation carrier showed that the substitution co-segregated with VSD. The p.R43W variant was predicted to be a pathogenic mutation, and the functional analysis demonstrated that the GATA4 R43W mutant protein resulted in significantly decreased transcriptional activity compared with its wild-type counterpart. The findings expand the mutational spectrum of GATA4 linked to VSD and provide more insight into the molecular mechanism of VSD.


Genetics Transcription factor Ventricular septal defect 


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Yi-Qing Yang
    • 1
  • Li Li
    • 2
  • Juan Wang
    • 3
  • Xing-Yuan Liu
    • 4
  • Xiao-Zhong Chen
    • 5
  • Wei Zhang
    • 5
  • Xiao-Zhou Wang
    • 6
  • Jin-Qi Jiang
    • 7
  • Xu Liu
    • 8
  • Wei-Yi Fang
    • 8
  1. 1.Department of Cardiovascular ResearchShanghai Chest Hospital, Medical College of Shanghai Jiaotong UniversityShanghaiChina
  2. 2.Key Laboratory of Arrhythmias, Ministry of EducationTongji University School of MedicineShanghaiChina
  3. 3.Department of CardiologyEast Hospital, Tongji University School of MedicineShanghaiChina
  4. 4.Department of PediatricsTongji Hospital, Tongji University School of MedicineShanghaiChina
  5. 5.Department of Cardiac SurgeryShanghai Chest Hospital, Medical College of Shanghai Jiaotong UniversityShanghaiChina
  6. 6.Department of Pediatric Cardiac SurgeryShanghai Chest Hospital, Medical College of Shanghai Jiaotong UniversityShanghaiChina
  7. 7.Department of EmergencyShanghai Chest Hospital, Medical College of Shanghai Jiaotong UniversityShanghaiChina
  8. 8.Department of CardiologyShanghai Chest Hospital, Medical College of Shanghai Jiaotong UniversityShanghaiChina

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