Key Laboratory of Clinical Laboratory Medicine of GuangxiDepartment of EducationDepartment of Clinical Laboratory, the First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Department of Laboratory Medicine, Guangxi Hospital Division of The First Affiliated Hospital, Sun Yat-Sen University, Nanning, Guangxi, China.
J Hematop. 2023 Jun;16(2):95-101. doi: 10.1007/s12308-023-00545-8. Epub 2023 May 5.
Hereditary spherocytosis (HS) is a common, hereditary hemolytic anemia (HHA) that is attributed to the disturbance of five erythrocyte membrane proteins. HS is also common in Guangxi, China. Target region capture high-throughput sequencing technology was used to analyze genetic mutations found in HS patients. Pedigree analysis was also performed, in some cases, to provide an optimized approach for the etiological diagnosis of complex, hereditary hemolytic anemia. Blood samples from the probands and their families were assessed by laboratory tests, target region capture high-throughput sequencing technology, and Sanger sequencing. We detected 79 HS patients from 37 unrelated families. The mutations observed in these patients were found mainly in four HS-related genes. These included SLC4A1, which was mutated in 31.65% of patients (25/79), SPTA1 (30.78% (24/79)), EPB42 (6.33% (5/79)), and SPTB (5.06% (4/79)). Composite genotype was observed in 26.58% (21/79) of patients and included mutations in two or more HS-related genes or mutations in HS-related genes combined with thalassemia or G6PD deficiency. No significant differences in clinical symptoms were found among patients of various genotypes except total bilirubin. Mean reticulocyte volume (MRV) and mean sphered cell volume (MSCV) of the composite genotype were significantly different from other groups. A total of 28 mutation types were found in HS-related genes. Using high-throughput sequencing technology, we also found some cases that had been misdiagnosed. MRV and MSCV are more significant in compound mutations as sensitive determinants of HS. High-throughput sequencing technology can be used to provide a more effective etiological diagnostic method for HS, with high efficiency and specificity.
遗传性球形红细胞增多症（HS）是一种常见的遗传性溶血性贫血（HHA），其病因是红细胞膜蛋白的五种紊乱。HS 在我国广西也很常见。我们采用靶向区域捕获高通量测序技术分析 HS 患者的基因突变。对某些病例进行家系分析，为复杂遗传性溶血性贫血的病因诊断提供了一种优化方法。通过实验室检查、靶向区域捕获高通量测序技术和 Sanger 测序对先证者及其家系的血液样本进行评估。我们从 37 个无关家庭中发现了 79 名 HS 患者。在这些患者中观察到的突变主要发生在四个 HS 相关基因中。这些基因包括 SLC4A1（31.65%（25/79））、SPTA1（30.78%（24/79））、EPB42（6.33%（5/79））和 SPTB（5.06%（4/79））。在 26.58%（21/79）的患者中观察到复合基因型，包括两个或更多 HS 相关基因的突变或 HS 相关基因与地中海贫血或 G6PD 缺乏症的突变相结合。除总胆红素外，不同基因型患者的临床症状无明显差异。复合基因型的平均网织红细胞体积（MRV）和平均球形红细胞体积（MSCV）与其他组明显不同。在 HS 相关基因中发现了 28 种突变类型。使用高通量测序技术，我们还发现了一些误诊的病例。MRV 和 MSCV 在复合突变中作为 HS 的敏感决定因素更为显著。高通量测序技术可用于 HS 提供更有效、更特异的病因诊断方法。
