Chen Xin, Jiang Chunxue, Song Wenliang, Sun Tingting, Yan Jingli, Xu Wei, You Kai
Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China.
Front Immunol. 2024 Dec 10;15:1498066. doi: 10.3389/fimmu.2024.1498066. eCollection 2024.
Mutations in the recombination-activating gene 1, a pivotal component essential for V(D)J recombination and the formation of T- and B-cell receptors, can result in autoimmune hemolytic anemia, a rare hematological condition characterized by the autoantibody-mediated destruction of red blood cells. Herein, we report the case of a 1-year-and-4-month-old girl who presented with progressively aggravated anemia, fever, and cough. Autoimmune hemolytic anemia was confirmed by bone marrow aspiration and Coombs test. During treatment, the patient experienced two episodes of severe pneumonia and respiratory failure. Next-generation metagenomic sequencing of sputum samples confirmed the presence of cytomegalovirus and infections. Additionally, lymphocyte subset analysis revealed a T-B+ immunodeficiency. Whole exome and Sanger sequencing revealed a pathogenic recombinase-activating gene 1 mutation (c.2095C>T, p.Arg699Trp) and a likely pathogenic variant (c.2690G>A, p.Arg897Gln), resulting in a missense mutation in the amino acid sequence of the coding protein. Consequently, the patient was diagnosed with a recombination-activating gene 1 mutation and autoimmune hemolytic anemia as the initial presentation. This study reports a case of a recombination-activating gene 1 mutation in China and documents a combination of mutation sites and associated clinical phenotypes that were previously unreported. In this study, we outline the diverse clinical phenotypes observed in cases of recombination-activating gene 1 mutations presenting with autoimmune hemolytic anemia, aiming to facilitate timely diagnosis and appropriate treatment.
重组激活基因1发生突变，该基因是V(D)J重组以及T细胞和B细胞受体形成所必需的关键成分，可导致自身免疫性溶血性贫血，这是一种罕见的血液疾病，其特征是自身抗体介导的红细胞破坏。在此，我们报告一例1岁4个月大的女童，她出现进行性加重的贫血、发热和咳嗽。骨髓穿刺和库姆斯试验确诊为自身免疫性溶血性贫血。治疗期间，该患者经历了两次严重肺炎和呼吸衰竭。痰标本的二代宏基因组测序证实存在巨细胞病毒和感染。此外，淋巴细胞亚群分析显示T-B+免疫缺陷。全外显子组测序和桑格测序揭示了一个致病的重组酶激活基因1突变（c.2095C>T，p.Arg699Trp）和一个可能致病的变异（c.2690G>A，p.Arg897Gln），导致编码蛋白的氨基酸序列发生错义突变。因此，该患者被诊断为重组激活基因1突变，初始表现为自身免疫性溶血性贫血。本研究报告了中国一例重组激活基因1突变病例，并记录了以前未报告的突变位点和相关临床表型的组合。在本研究中，我们概述了在伴有自身免疫性溶血性贫血的重组激活基因1突变病例中观察到的多种临床表型，旨在促进及时诊断和适当治疗。
