Whole-exome sequencing identifies SGCD and ACVRL1 mutations associated with total anomalous pulmonary venous return (TAPVR) in Chinese population

// Jun Li 1, * , Shiwei Yang 1, * , Zhening Pu 2, * , Juncheng Dai 2 , Tao Jiang 2 , Fangzhi Du 2 , Zhu Jiang 2 , Yue Cheng 2 , Genyin Dai 1 , Jun Wang 1 , Jirong Qi 3 , Liming Cao 1 , Xueying Cheng 1 , Cong Ren 1 , Xinli Li 4 , Yuming Qin 1 1 Department of Cardiology, Children's Hospital of Nanjing Medical University, Nanjing 210008, China 2 Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing 211166, China 3 Department of Cardiothoracic Surgery, Children's Hospital of Nanjing Medical University, Nanjing 210008, China 4 Department of Cardiology, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China * These authors contributed equally to this work Correspondence to: Shiwei Yang, email: jrdoctoryang@163.com Yuming Qin, email: doctor025ym@163.com Xinli Li, email: xinli3267@yeah.net Keywords: total anomalous pulmonary venous return (TAPVR), genetics, whole-exome sequencing (WES), rare genetic variant, congenital disease Received: August 01, 2016      Accepted: February 06, 2017      Published: February 17, 2017 ABSTRACT As a rare type of Congenital Heart Defects (CHD), the genetic mechanism of Total Anomalous Pulmonary Venous Return (TAPVR) remains unknown, although previous studies have revealed potential disease-driving regions/genes. Blood samples collected from the 6 sporadic TAPVR cases and 81 non-TAPVR controls were subjected to whole exome sequencing. All detected variations were confirmed by direct Sanger sequencing. Here, we identified 2 non-synonymous missense mutations: c.C652T, p.R218W in activin A receptor type II-like 1 (ACVRL1), c.C717G, p.D239E in sarcoglycan delta (SGCD). Our results offered the landscape of mutations for TAPVR in Chinese population firstly and are valuable in the mutation-based pre- and post-natal screening and genetic diagnosis for TAPVR.