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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2018.00559

Rare copy number variants identify novel genes in sporadic total anomalous pulmonary vein connection

 Xin Shi1, Liangping Chen1, Xianting Jiao1, Zixiong Li2, Bo Chen1, Gang Liu3, Jing Wang1, Yuejuan Xu1, Jing Sun1, Qihua Fu3, Yanan Lu1 and Chen Sun1*
  • 1Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, China
  • 281th Hospital of PLA, China
  • 3Shanghai Children's Medical Center, China

Total anomalous pulmonary venous connection (TAPVC) is characterized as a rare cyanotic congenital heart defect (CHD). Several genes have been associated with TAPVC but the underlying etiology and mechanisms in most cases remain elusive. To search novel variants and candidate genes, we screened a cohort of 78 TAPVC cases and 100 controls for rare copy number variants (CNV). Then we identified pathogenic CNVs by statistical comparisons between the case and control groups. We identified altogether 8 pathogenic CNVs of 7 candidate genes (PCSK7, RRP7A, SERHL, TARP, TTN, SERHL2, NBPF3). All these 7 genes have not been described previously to be associated with TAPVC. After network analysis of these candidate genes and 27 known pathogenic genes derived from the literature and publicly available database, PCSK7 and TTN had been most strongly linked to TAPVC. Our study provides novel candidate genes potentially related to this rare congenital birth defect that should be further fundamentally researched and discloses the possible molecular pathogenesis of TAPVC.

Keywords: congenital heart defects, Total anomalous pulmonary venous connection, Whole-exome sequencing, copy number variants, Pathogenesis

Received: 29 Aug 2018; Accepted: 02 Nov 2018.

Edited by:

Tao Huang, Shanghai Institutes for Biological Sciences (CAS), China

Reviewed by:

Daizhan Zhou, bio-x institute, Shanghai jiaotong university
Yujun Shen, Tianjin Medical University, China  

Copyright: © 2018 Shi, Chen, Jiao, Li, Chen, Liu, Wang, Xu, Sun, Fu, Lu and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Chen Sun, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China, chensun@xinhuamed.com.cn