Pediatric Cardiology

, Volume 32, Issue 2, pp 193–201

Novel NKX2-5 Mutations in Patients With Familial Atrial Septal Defects

  • Xing-Yuan Liu
  • Juan Wang
  • Yi-Qing Yang
  • Yang-Yang Zhang
  • Xiao-Zhong Chen
  • Wei Zhang
  • Xiao-Zhou Wang
  • Jing-Hao Zheng
  • Yi-Han Chen
Original Article

DOI: 10.1007/s00246-010-9859-6

Cite this article as:
Liu, XY., Wang, J., Yang, YQ. et al. Pediatr Cardiol (2011) 32: 193. doi:10.1007/s00246-010-9859-6

Abstract

Atrial septal defect (ASD) is a common cardiovascular malformation and an important contributor to substantial morbidity and mortality. Increasing evidence demonstrates that mutated NKX2-5, a gene encoding a homeobox transcription factor crucial to cardiogenesis, is a significant genetic determinant for congenital ASD. Nevertheless, the genetic basis for ASD in a majority of ASD patients remains largely unknown. In the current study, the entire coding region of NKX2-5 was sequenced initially for 58 unrelated probands with familial ASD. The relatives of the probands harboring identified mutations and 200 unrelated control individuals were subsequently genotyped. Three novel heterozygous NKX2-5 mutations (p.P43GfsX59, p.C46 W, and p.S179F) were identified respectively in three families with autosomal dominantly inherited ASD. These mutations, absent in 200 control individuals, cosegregated with ASD in the families that had complete penetrance. The findings expand the spectrum of mutations in NKX2-5 linked to ASD and contribute to genetic counseling, clinical interventions, and prenatal prevention of ASD for individuals with genetic susceptibility.

Keywords

Atrial septal defect Genetics Transcription factor 

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Xing-Yuan Liu
    • 1
  • Juan Wang
    • 2
  • Yi-Qing Yang
    • 3
  • Yang-Yang Zhang
    • 4
  • Xiao-Zhong Chen
    • 5
  • Wei Zhang
    • 5
  • Xiao-Zhou Wang
    • 5
  • Jing-Hao Zheng
    • 6
  • Yi-Han Chen
    • 2
  1. 1.Department of PediatricsTongji Hospital, Tongji University School of MedicineShanghaiChina
  2. 2.Department of CardiologyEast Hospital, Tongji University School of MedicineShanghaiChina
  3. 3.Department of Cardiovascular ResearchShanghai Chest Hospital, Medical College of Shanghai Jiaotong UniversityShanghaiChina
  4. 4.Department of CardiologyFirst Affiliated Hospital of Nanjing Medical UniversityNanjingChina
  5. 5.Department of Cardiac SurgeryShanghai Chest Hospital, Medical College of Shanghai Jiaotong UniversityShanghaiChina
  6. 6.Department of Pediatric Thoracic and Cardiovascular SurgeryShanghai Children’s Medical Center, Medical College of Shanghai Jiaotong UniversityShanghaiChina