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

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.

A Novel ANK1 Mutation in a Neonatal Hereditary Spherocytosis Case: Diagnostic Challenges and Familial Genetic Analysis

“…First, the proband did not have abnormal parameters throughout the course of the disease as outlined in the HS diagnosis and treatment guidelines (2011 Edition), in which spherical erythrocytes and MCHC were used as important indicators for neonatal diagnosis [8]. In other studies, there were no abnormal indicators of MCHC in some neonatal HS cases, suggesting that this indicator may not apply to neonatal cases [10, 12, 13]. Second, by inquiring about family history, it was found that some members of different ages in the family of the proband had histories of jaundice, anemia, and splenomegaly.…”

“…According to the different pathological genes and incidence rates, HS mostly follows an autosomal dominant inheritance model. ANK1 , the main pathogenic gene of HS, has approximately 80 variants reported in the Chinese population, of which nearly 80% are loss of function variants (including the nonsense mutation group and frameshift mutation group) and splicing mutation groups affecting transcription [12, 13]. However, Qin et al [14] found that there was no significant difference in the severity of disease phenotypes between different groups.…”

A large family of hereditary spherocytosis and a rare case of hereditary elliptocytosis with a novel SPTA1 mutation underdiagnosed in Taiwan: A case report and literature review

“…[15] In studies, ANK1 mutations (about 50%) are most commonly present, followed by SPTB mutations (about 30%). [16][17][18][19][20][21] But some investigations reported that Chinese HS patients are affected by band 3 deficiency. Because of the small number of reported cases, it is necessary to collect more data to determine the actual rates of erythrocyte membrane protein deficiency in Chinese HS patients.…”

Novel SPTB frameshift mutation in a Chinese neonatal case of hereditary spherocytosis type 2: A case report

“…In addition, according to guidelines for the diagnosis and management of HS (2011 update), HS may be suspected when the mean corpuscular hemoglobin concentration (MCHC) in newborns exceeds 360 g/l (5). However, according to the reported Asian cases, an increase in MCHC is not common in neonatal HS (3,(6)(7)(8). This may be due to differences in ethnic background or statistical errors caused by lower numbers of neonatal cases.…”