AUTHOR=Wang Dong , Song Li , Shen Li , Zhang Kaihui , Lv Yuqiang , Gao Min , Ma Jian , Wan Ya , Gai Zhongtao , Liu Yi 

TITLE=Mutational Characteristics of Causative Genes in Chinese Hereditary Spherocytosis Patients: a Report on Fourteen Cases and a Review of the Literature

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.644352

DOI=10.3389/fphar.2021.644352

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Hereditary spherocytosis (HS), characterized by the presence of spherocytic red cells in peripheral blood, hemolysis, splenomegaly, jaundice, and gallstones, is a common form of inherited hemolytic anemia (HA). To date, five causative genes associated with HS have been identified, including <italic>ANK1, SPTB, SPTA1, SLC4A1</italic>, and <italic>EPB42</italic>.</p><p><bold>Methods:</bold> Clinically suspected patients with HS or undiagnosed HA from 14 Chinese families were enrolled in this study. We presented the patients’ clinical features and identified the causative gene variants in these patients using whole exome sequencing (WES), with 10 novel and four reported mutations in the <italic>ANK1</italic> and <italic>SPTB</italic> genes (seven mutations in <italic>ANK1</italic> and seven in <italic>SPTB</italic>), individually. Then, we reviewed all available literature on Chinese HS patients from 2000 to 2020 in PubMed and Chinese Journals with genetic results and clinical information, to delineate gene mutation spectrum and potential correlation with phenotypes.</p><p><bold>Results:</bold> A total of 158 variants (including 144 in previous reports and 14 in this study) indicated that <italic>ANK1</italic> (46%) and <italic>SPTB</italic> (42%) were the most frequently mutated genes in Chinese HS patients, followed by <italic>SLC4A1</italic> (11%) <italic>and SPTA1</italic> (1%), while no mutations in <italic>EPB42</italic> was reported. Most of the mutations in <italic>ANK1</italic> and <italic>SPTB</italic> were nonsense (26/73 in <italic>ANK1</italic> and 32/66 in <italic>SPTB</italic>) and frameshift (20/73 in <italic>ANK1</italic> and 15/66 in <italic>SPTB</italic>), while missense mutations (14/18) accounted for the majority in <italic>SLC4A1</italic>. The higher mutation frequency of <italic>ANK1</italic> was found in its exon 8, 9, 26, and 28. The majority of mutations in <italic>SPTB</italic> were located in its exon 13, 15, and 18–30, whereas mutations in <italic>SLC4A1</italic> were scattered throughout the entire region of the gene.</p><p><bold>Conclusion:</bold> Our study expanded the mutation spectrum of <italic>ANK1</italic> and <italic>SPTB</italic>. Furthermore, we clarified the mutational characteristics of causative genes by reviewing all available literature on Chinese patients with HS.</p>