遗传性球形红细胞增多症3例全外显子组基因测序报道

沈克锋.遗传性球形红细胞增多症3例全外显子组基因测序报道[J].内科急危重症杂志,2024,30(3):219-223

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DOI：10.11768/nkjwzzzz20240305

中文关键词: 遗传性球形红细胞增多症全外显子组测序基因突变发病机制临床表现遗传咨询

英文关键词:

基金项目:国家自然科学基金面上项目（82270203）

作者	单位
沈克锋	华中科技大学同济医学院附属同济医院

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中文摘要:

摘要的：探讨遗传性球形红细胞增多症（HS）的分子致病机制、临床表现、治疗管理及全外显子组测序（WES）技术的应用价值。方法：采用WES技术对3例HS患者进行基因变异检测，依据美国医学遗传学与基因组学学会（ACMG）指南对变异进行致病性评估。查阅HS相关最新文献，对其分子机制、临床表型和治疗管理进行系统综述。结果：3例患者的临床表现（贫血、黄疸、脾肿大）和主要实验室检测结果（如外周血涂片见球形红细胞明显增多）符合典型HS特征，WES分别检测出SLC4A1（p.R808H）、SPTB（p.Y1606*）、SPTA1（p.L2380R）基因突变，口腔黏膜脱落细胞Sanger测序验证均证实为胚系杂合突变，依据ACMG指南均归为致病性突变，其中SPTB（p.Y1606*）和SPTA1（p.L2380R）突变属于新发现的致病突变，丰富了相关基因致病突变谱范围。结论：WES技术可发现新的致病基因突变，在HS的分子诊断、治疗管理和遗传咨询等方面发挥重要作用。

英文摘要:

Abstract Objective: To investigate the molecular pathogenesis, clinical manifestations and therapeutic management of hereditary spherocytosis (HS) and the value of whole exome sequencing (WES). Methods: WES technology was used to detect genetic variants in suspected HS patients, and variants were evaluated for pathogenicity according to the American College of Medical Genetics and Genomics (ACMG) guideline. The latest literature related to HS was reviewed to provide a systematic review of the molecular mechanisms, clinical phenotypes and therapeutic management. Results: Clinical manifestations (anemia, jaundice, splenomegaly) and major laboratory test results (e.g., markedly increased spherical red blood cells seen in peripheral blood smears) of the 3 patients were consistent with typical HS features, and mutations in the SLC4A1 (p.R808H), SPTB (p.Y1606*), and SPTA1 (p.L2380R) genes were detected by WES, respectively, and Sanger sequencing validation using exfoliated buccal mucosal cells confirmed that all of them were germline heterozygous mutations, and the 3 mutations were classified as pathogenic mutations according to the ACMG guideline. Additionally, the SPTB (p.Y1606*) and SPTA1 (p.L2380R) mutations were newly discovered pathogenic mutations, which expanded the pathogenic mutation spectrum of the related genes. Conclusion: WES can identify novel pathogenic mutations and play an important role in molecular diagnosis, therapeutic management and genetic counseling of HS.