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Identification of rare variants in novel candidate genes in pulmonary atresia patients by next generation sequencing

  • Shi, Xin1
  • Zhang, Li2
  • Bai, Kai1
  • Xie, Huilin1
  • Shi, Tieliu3
  • Zhang, Ruilin4
  • Fu, Qihua5
  • Chen, Sun1
  • Lu, Yanan1
  • Yu, Yu1, 6
  • Sun, Kun1
  • 1 Department of Pediatric Cardiovascular, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China
  • 2 Key Laboratory of Advanced Theory and Application in Statistics and Data Science, East China Normal University, Ministry of Education, Shanghai, China
  • 3 The Center for Bioinformatics and Computational Biology, Shanghai Key Laboratory of Regulatory Biology, the Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China
  • 4 School of Life Sciences, Fudan University, Shanghai 200438, China
  • 5 Medical Laboratory, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
  • 6 Institute for Developmental and Regenerative Cardiovascular Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China
Published Article
Computational and Structural Biotechnology Journal
Publication Date
Feb 12, 2020
DOI: 10.1016/j.csbj.2020.01.011
PMID: 32128068
PMCID: PMC7044470
PubMed Central


Pulmonary atresia (PA) is a rare congenital heart defect (CHD) with complex manifestations and a high mortality rate. Since the genetic determinants in the pathogenesis of PA remain elusive, a thorough identification of the genetic factors through whole exome sequencing (WES) will provide novel insights into underlying mechanisms of PA. We performed WES data from PA/VSD (n = 60), PA/IVS (n = 20), TOF/PA (n = 20) and 100 healthy controls. Rare variants and novel genes were identified using variant-based association and gene-based burden analysis. Then we explored the expression pattern of our candidate genes in endothelium cell lines, pulmonary artery tissues, and embryonic hearts. 56 rare damage variants of 7 novel candidate genes ( DNAH10, DST, FAT1, HMCN1, HNRNPC, TEP1, and TYK2 ) were certified to have function in PA pathogenesis for the first time. In our research, the genetic pattern among PA/VSD, PA/IVS and TOF/PA were different to some degree. Taken together, our findings contribute new insights into the molecular basis of this rare congenital birth defect.

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