Identification of a novel de novo ANK1 R1426* nonsense mutation in a Chinese family with hereditary spherocytosis by NGS

// Xiong Wang 1, * , Bin Yi 2, * , Ketao Mu 3 , Na Shen 1 , Yaowu Zhu 1 , Qun Hu 4 and Yanjun Lu 1 1 Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China 2 Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China 3 Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China 4 Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China * These authors contributed equally to this work Correspondence to: Qun Hu, email: qunhu2010@163.com Yanjun Lu, email: junyanlu_2000@163.com Keywords: hereditary spherocytosis, splenectomy, anemia, ankyrin, mutation Received: April 14, 2017 Accepted: May 15, 2017 Published: May 27, 2017 ABSTRACT Hereditary spherocytosis (HS) is an inherited heterogeneous hemolytic anemia, characterized by the presence of spherical-shaped erythrocytes on the peripheral blood smear, and the clinical manifestation ranges from asymptomatic to severely anemic, and transfusion-dependent patients. Mutations in at least five genes (ANK1, EPB42, SLC4A1, SPTA1, and SPTB) have been identified so far, and mutations of ANK1 gene are responsible for the majority of all HS cases. In this study, targeted next generation sequencing (NGS) was applied to identify a novel de novo ANK1 c.4276C>T (p.R1426*) nonsense mutation in a Chinese family with a patient of HS who was diagnosed clinically with only 10% spherical-shaped erythrocytes in the peripheral blood and received splenectomy. Sanger sequencing further confirmed that only the patient carried heterozygous ANK1 c.4276C>T nonsense mutation, while none of his parents or his young brother carried this mutation. Moreover, consistent with the genetic findings, the anemia was ameliorated after splenectomy. RBCs increased from 2.74 × 1012/L pre-surgery to 4.76 × 1012/L one month post-surgery, and hemoglobin increased from 66g/L to 126g/L respectively. This is the first report of ANK1 c.4276C>T (p.R1426*) heterozygous nonsense mutation responsible for HS. Our results also demonstrate that targeted NGS may provide a powerful approach for rapid genetic test of HS.