Department of Hematology, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Department of Hematology & Oncology, Chengdu Women's and Children's Central Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, People's Republic of China.
Clin Genet. 2022 Dec;102(6):474-482. doi: 10.1111/cge.14223. Epub 2022 Sep 26.
Hereditary spherocytosis (HS) is a prevalent inherited hemolytic disorder primarily reported in Caucasians. Recently, next-generation sequencing (NGS) techniques have shown tremendous potential in the diagnosis of HS. HS commonly originates from variants in ANK1, SPTB, SLC4A1, SPTA1, and EPB42. This review is focused on 13 previous clinical studies on genotype-phenotype correlation, which might promote the role of causative variants in the diagnosis and prognosis of HS. Most studies have focused on the pediatric population and Asian countries. The occurrence of novel variants was common in each cohort, and variants with a high frequency of causative genes were demonstrated. In conclusion, patients with variants in SPTA1 and SLC4A1 were reported to have more severe and milder anemia, respectively. ANK1 and SPTB are the most common variants in patients with HS, and no significant difference in phenotypes was observed between patients with variants in ANK1 versus SPTB. The types and locations of variants might influence the phenotype of each genotype, whereas the roles of concomitant pathogenic genes and the source of variants deserve further investigation.
遗传性球形红细胞增多症（HS）是一种常见的遗传性溶血性疾病，主要见于高加索人群。最近，下一代测序（NGS）技术在 HS 的诊断中显示出巨大的潜力。HS 通常源于 ANK1、SPTB、SLC4A1、SPTA1 和 EPB42 中的变异。本综述重点介绍了 13 项关于基因型-表型相关性的临床前研究，这些研究可能促进了致病变异在 HS 诊断和预后中的作用。大多数研究都集中在儿科人群和亚洲国家。每个队列中都经常出现新的变异，并且表现出高频率的致病基因变异。总之，在 SPTA1 和 SLC4A1 中存在变异的患者报告有更严重和更轻微的贫血。ANK1 和 SPTB 是 HS 患者中最常见的变异，ANK1 与 SPTB 中存在变异的患者之间的表型无显著差异。变异的类型和位置可能会影响每个基因型的表型，而同时存在的致病基因的作用和变异的来源值得进一步研究。
