Preliminary Study on the Clinical and Genetic Characteristics of Hereditary Spherocytosis in 15 Chinese Children.

Chunlei Zhan,Feng Chen,Zhongjin Xu,Yu Yang,Yao Ye,Hong Wang,Chongjun Wu,Ting Xiong

doi:10.3389/fgene.2021.652376

Abstract

ObjectiveTo investigate the clinical and genetic characteristics of hereditary spherocythemia (HS) in Chinese children, and to analyze the potential genotypic/phenotypic associations.MethodsThe clinical data and gene test results of children with HS were collected. All patients were diagnosed by gene test results, and the laboratory results were obtained before splenectomy. The data of red blood cell (RBC), hemoglobin (HB), mean red blood cell volume (MCV), mean red blood cell hemoglobin (MCH), mean red blood cell hemoglobin concentration (MCHC), and hematocrit (HCT) were statistically analyzed according to different mutation genes. Statistical methods for comparison between groups Mann–Whitney test analysis, two-terminal p < 0.05 was considered significant difference.ResultsA total of 15 children were enrolled in our hospital, and 14 variants were found (nine variants have not been reported before), including 10 ANK1 mutations (seven ANK1 truncated mutations) and five SPTB mutations. Patients with ANK1 mutations had more severe anemia than those with SPTB mutations (significantly lower RBC, HB, MCHC, and HCT).ConclusionThis is one of the few studies on the genetic and clinical characteristics of children with HS in China. This study identified the unique genetic and clinical characteristics of Chinese children with HS and analyzed the pathogenic genotype–phenotypic association. The results confirmed that the anemia degree of HS patients caused by ANK1 was more serious than that of patients with SPTB deficiency. However, further study of the correlation between genotype and phenotype requires a larger sample size.

Highlights

Hereditary spherocytosis (HS) is a genetic disease and the most common cause of congenital hemolytic anemia (HA) (Perrotta et al, 2008)
Some of these children needed to be treated with blood transfusion, and some of them were given symptomatic treatment such as antibiotic during hospitalization due to the presence of infection (Supplementary Materials 1, 2)
As for whether splenectomy was needed, we planned to conduct further follow-up and make a comprehensive judgment in the later stage based on factors such as spleen size, transfusion demand and age

Summary

Introduction

Hereditary spherocytosis (HS) is a genetic disease and the most common cause of congenital hemolytic anemia (HA) (Perrotta et al, 2008). The clinical manifestations of HS vary greatly, ranging from asymptomatic to severe hemolysis. The typical clinical manifestations are similar to other hemolytic anemias, characterized by anemia, jaundice, and HS in Chinese Children splenomegaly(Hassoun and Palek, 1996). With the widespread use of genetic diagnostic techniques, many new mutations have been discovered in genes associated with HS, including ANK1, SPTB, SLC4A1, SPTA1, and EPB42 (Eber et al, 1996). These five HS related genes involved in the interaction of double red cell membrane and lipids, its coding respectively ankyrin, β/α-spectrin, band 3, and protein 4.2. Band 3, and protein 4.2 are the components of “band 3 complex” involving in transmembrane protein linkage, and spectrin is a component of cell membrane skeleton (Delaunay, 2007; Da et al, 2013)

Methods

Results

Discussion

Conclusion