Wang Wen-Juan, Xie Jun-Dan, Yao Hong, Ding Zi-Xuan, Jiang Ai-Rui, Ma Liang, Shen Hong-Jie, Chen Su-Ning
National Clinical Research Center for Hematologic Diseases, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Suzhou, China.
Clin Genet. 2023 Jan;103(1):67-78. doi: 10.1111/cge.14244. Epub 2022 Oct 21.
Hereditary spherocytosis (HS) is the most common type of hereditary erythrocyte membrane disease and has varied phenotypic features and genetic patterns. We herein performed a retrospective study of 94 patients with HS and aimed to investigate the genetic variations and genotype-phenotype correlations using targeted next-generation sequencing. In 79/94 (84%) patients, 83 HS variants including 67 novel variants were identified. Pathogenic variants of SPTB, ANK1, SLC4A1, SPTA1, and EPB42 were found in 32/79(41%), 22/79(28%), 15/79 (19%), 8/79 (9%), and 3/79 (4%) of the patients respectively, revealing that SPTB is the most frequently mutated HS gene in Eastern China. Most SPTB and ANK1 gene variations were nonsense and frameshift variations. Missense variants were the main variant type of SLC4A1, SPTA1, and EPB42 genes. Interestingly, one SPTA1 variant (p. Arg1757Cys) showed an autosomal dominant inheritance pattern and one EPB42 variant (p. Gln377His) was apparent as a hotspot variation. Furthermore, genotype-phenotype analysis was performed among the five mutated gene groups. Besides the finding that patients with the SLC4A1 variant had the highest mean corpuscular hemoglobin levels, no clear correlations between genotype and phenotype were observed.
遗传性球形红细胞增多症（HS）是最常见的遗传性红细胞膜疾病类型，具有多种表型特征和遗传模式。我们在此对94例HS患者进行了一项回顾性研究，旨在使用靶向二代测序技术研究基因变异以及基因型与表型的相关性。在79/94（84%）例患者中，共鉴定出83个HS变异，其中包括67个新变异。分别在32/79（41%）、22/79（28%）、15/79（19%）、8/79（9%）和3/79（4%）的患者中发现了SPTB、ANK1、SLC4A1、SPTA1和EPB42的致病变异，这表明SPTB是中国东部地区最常发生突变的HS基因。大多数SPTB和ANK1基因变异为无义变异和移码变异。错义变异是SLC4A1、SPTA1和EPB42基因的主要变异类型。有趣的是，一个SPTA1变异（p.Arg1757Cys）表现出常染色体显性遗传模式，一个EPB42变异（p.Gln377His）表现为热点变异。此外，对五个突变基因组进行了基因型-表型分析。除了发现携带SLC4A1变异的患者平均红细胞血红蛋白水平最高外，未观察到基因型与表型之间存在明确的相关性。
