# Clinical Characteristics and Gene Mutations of Hereditary Spherocytosis in 59 Chinese Children

## TL;DR

This study examines the genetic and clinical features of hereditary spherocytosis in 59 Chinese children, identifying key mutations and their effects on disease severity.

## Contribution

The study expands the mutation spectrum of hereditary spherocytosis in Chinese pediatric patients and highlights sex and mutation-type differences in clinical outcomes.

## Key findings

- ANK1 and SPTB gene mutations were the primary causes of hereditary spherocytosis in the studied population.
- Missense and frameshift mutations were most common, with de novo mutations observed in over 60% of patients.
- ANK1 mutations were associated with more severe anemia compared to SPTB mutations.

## Abstract

Hereditary spherocytosis (HS) is a common disease in hereditary hemolytic anemia. Advancements in sequencing technology have enabled the identification of a growing number of mutation sites associated with HS. This study analyzed the clinical characteristics and gene mutations of HS in our center.

Retrospective collection of data on 59 Chinese pediatric patients with HS admitted to the Hematology Department of Chongqing Medical University Affiliated Children's Hospital from 2013 to 2022. Second‐generation gene sequencing was performed on participants, with verification of detected variants using Sanger sequencing. Data analysis was conducted using various databases, and statistical methods were used for differential analysis.

We collected clinical data of 59 Chinese children with HS phenotype, including 27 males (45.8%) and 32 females (54.2%), all unrelated. The age of onset ranged from 0 to 180 months, with a median age of 60 months. Our study found that ANK1 and SPTB gene mutations were the primary causes of HS, with missense and frameshift mutations being the most common. De novo mutations were present in 37 (62.7%) patients, while the remaining mutations were inherited. We noted a higher proportion of females (p = 0.032) and lower total bilirubin levels (p = 0.014) in patients with multiple gene mutations. Patients with ANK1 gene mutations experienced more severe anemia compared to those with SPTB gene mutations (p = 0.041). Additionally, there were significant differences in mean corpuscular hemoglobin concentration (MCHC) between different mutation types (p = 0.036), indicating lower MCHC levels in the missense mutation group. No differences in clinical phenotypes were observed among different structural domains of ANK1 and SPTB mutations. Splenectomy significantly alleviated the symptoms in HS patients.

We identified unique genetic and clinical characteristics mutations of HS in Chongqing, China. These findings expand the mutation spectrum of HS and have implications for early diagnosis and treatment of the disease.

Summary of the causative genes' spectrum of 59 Chinese HS Children patients. The schematic diagram of ankyrin, β‐spectrin, α‐spectrin, and band three protein domains with ANK1, SPTB, SPTA1, and SLC4A1 mutations. Distribution of mutations in the exons of ANK1 and SPTB genes.