Genetic and Clinical Characteristics of Patients With Hereditary Spherocytosis in Hubei Province of China

Abstract

Hereditary spherocytosis (HS) is an inherited disorder characterized by anemia, splenomegaly, and spherical-shaped erythrocytes, caused by mutations in erythrocyte membrane Protein Genes ( ANK1 , SPTB , SLC4A1 , SPTA1 , and EPB42 ). We investigated molecular spectrum and genotype-phenotype correlation in HS patients in Hubei province, central China. Twenty-three patients with HS were included. A next-generation sequencing (NGS) panel targeting ANK1 , SPTB , SLC4A1 , SPTA1 , and EPB42 genes was used to screen potential variants. Sanger sequencing was applied to validate variants. Of the twenty-three patients, thirteen patients carried ANK1 variants, and ten patients harbored SPTB variants, including ten non-sense, six indel, four splice site, one start-loss, and one missense variant. Four out of twenty-two variants in our study were known, and eighteen variants were novel. Most ANK1 and SPTB variants were indel (5/12) or non-sense (7/10), respectively. Family member analysis in thirteen families showed that six variants were de novo . Variable expressivities were observed in a pair of twins with ANK1 c.341C > T variant, and two unrelated patients both carried ANK1 c.2T > A variant. Genotype-phenotype analysis found no significant difference between ANK1 and SPTB regarding the levels of Hb, RBC, MCV, MCH, and MCHC. However, variants in the ANK1 death domain were associated with lower levels of MCV and MCH compared to other ANK1 domains. In conclusion, NGS is a fast way to provide a molecular HS diagnosis. We also identified unique genetic and clinical characteristics of patients with HS in Hubei Province, China. However, a large sample size is needed to further investigate the genotype-phenotype correlation.

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

“…The study of Michaels et al showed that the MCHC of most HS cases was > 359 g/L ( Michaels et al, 1997 ). However, in our study, we found that 100% of patients had MCHC < 359 g/L, similar to the study of Wang ( Wang et al, 2020 ). In their report, it was found that 89% of patients (17/19) had MCHC < 35.9 g/dL, which further confirmed that MCHC has a poor measurement effect on HS.…”

“…Hb, RBC, and HCT of all patients without splenectomy were decreased. MCH and MCHC levels were within the normal range, which was similar to the recent studies in India and Hubei ( Aggarwal et al, 2020 ; Wang et al, 2020 ). The study of Michaels et al showed that the MCHC of most HS cases was > 359 g/L ( Michaels et al, 1997 ).…”

“…It was found that the MCHC levels of the nonsense group, frameshift group and splicing group were significantly higher than those of the missense group, while the severity of the disease was not significantly different between the different groups. Wang et al (2020) found no significant difference between patients with any SPTB variant. However, other groups are currently mixed with splenectomy/unresection, and the clinical manifestations of hemolytic anemia with obvious anemia can be eliminated by removing the spleen.…”

“…Also in China, Hubei province carried ANK1 (57%) and SPTB (43%) mutations ( Wang et al, 2020 ). Wang et al (2018) also found 45% ANK1 and 45% SPTB mutations.…”

“…However, only a few studies have been described in the Chinese population ( Wang et al, 2015 ). In several recent studies, Qin et al (2020) investigated 35 Chinese patients with clinical suspicion of HS, Wang et al (2020) studied 23 patients with HS, but few studies have reported on children alone and did not exclude splenectomy as a factor. This study summarized and analyzed the clinical and genetic characteristics of 15 children with HS before spleenectomy to investigate the laboratory characteristics and clinical relevance of the mutant gene or domain.…”