Whole exome sequencing identifies novel mutation in eight Chinese children with isolated tetralogy of Fallot

// Lin Liu 1, * , Hong-Dan Wang 2, * , Cun-Ying Cui 1 , Yun-Yun Qin 1 , Tai-Bing Fan 3 , Bang-Tian Peng 3 , Lian-Zhong Zhang 1 and Cheng-Zeng Wang 4 1 Department of Cardiovascular Ultrasound, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Zhengzhou 450003, China 2 Institute of Medical Genetics, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Zhengzhou 450003, China 3 Children’s Heart Center, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Zhengzhou 450003, China 4 Department of Ultrasound, The Affiliated Cancer Hospital, Zhengzhou University, Zhengzhou 450008, China * These authors have contributed equally to this work Correspondence to: Lin Liu, email: liulin_819@126.com Keywords: tetralogy of Fallot; congenital heart disease; whole exome sequencing Received: April 05, 2017 Accepted: September 05, 2017 Published: October 31, 2017 ABSTRACT Background: Tetralogy of Fallot is the most common cyanotic congenital heart disease. However, its pathogenesis remains to be clarified. The purpose of this study was to identify the genetic variants in Tetralogy of Fallot by whole exome sequencing. Methods: Whole exome sequencing was performed among eight small families with Tetralogy of Fallot. Differential single nucleotide polymorphisms and small InDels were found by alignment within families and between families and then were verified by Sanger sequencing. Tetralogy of Fallot-related genes were determined by analysis using Gene Ontology /pathway, Online Mendelian Inheritance in Man, PubMed and other databases. Results: A total of sixteen differential single nucleotide polymorphisms loci and eight differential small InDels were discovered. The sixteen differential single nucleotide polymorphisms loci were located on Chr 1, 2, 4, 5, 11, 12, 15, 22 and X. Among the sixteen single nucleotide polymorphisms loci, six has not been reported. The eight differential small InDels were located on Chr 2, 4, 9, 12, 17, 19 and X, whereas of the eight differential small InDels, two has not been reported. Analysis using Gene Ontology /pathway, Online Mendelian Inheritance in Man, PubMed and other databases revealed that PEX5 , NACA , ATXN2 , CELA1 , PCDHB4 and CTBP1 were associated with Tetralogy of Fallot. Conclusions: Our findings identify PEX5 , NACA , ATXN2 , CELA1 , PCDHB4 and CTBP1 mutations as underlying genetic causes of isolated tetralogy of Fallot.