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

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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.

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Acknowledgments

We are indebted to the participants for their dedication to the study. This project was made possible through grants from the Natural Science Fund of Shanghai, China (10ZR1433100), the National Natural Science Fund of China (30570768 and 30700776), and the National Basic Research Program of China (2010CB912604).

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Authors and Affiliations

  1. Department of Pediatrics, Tongji Hospital, Tongji University School of Medicine, Shanghai, China

    Xing-Yuan Liu

  2. Department of Cardiology, East Hospital, Tongji University School of Medicine, Shanghai, China

    Juan Wang & Yi-Han Chen

  3. Department of Cardiovascular Research, Shanghai Chest Hospital, Medical College of Shanghai Jiaotong University, 241 West Huaihai Road, Shanghai, 200030, China

    Yi-Qing Yang

  4. Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China

    Yang-Yang Zhang

  5. Department of Cardiac Surgery, Shanghai Chest Hospital, Medical College of Shanghai Jiaotong University, Shanghai, China

    Xiao-Zhong Chen, Wei Zhang & Xiao-Zhou Wang

  6. Department of Pediatric Thoracic and Cardiovascular Surgery, Shanghai Children’s Medical Center, Medical College of Shanghai Jiaotong University, Shanghai, China

    Jing-Hao Zheng

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  1. Xing-Yuan Liu
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  2. Juan Wang
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  3. Yi-Qing Yang
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  5. Xiao-Zhong Chen
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  7. Xiao-Zhou Wang
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Correspondence to Yi-Qing Yang.

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X.-Y. Liu and J. Wang contributed equally to this work.

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Liu, XY., Wang, J., Yang, YQ. et al. Novel NKX2-5 Mutations in Patients With Familial Atrial Septal Defects. Pediatr Cardiol 32, 193–201 (2011). https://doi.org/10.1007/s00246-010-9859-6

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  • DOI: https://doi.org/10.1007/s00246-010-9859-6

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