Department of Hematology and Oncology, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, No. 24, Lane 1400, Beijing West Road, Jing'an District, Shanghai, 200040, China.
Central Laboratory, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Ann Hematol. 2023 Nov;102(11):3177-3184. doi: 10.1007/s00277-023-05363-7. Epub 2023 Jul 18.
Cytopenia due to the abnormal regulation of GATA1 could manifest as varying degrees of thrombocytopenia and/or anemia and more severely in male children than in female children. Here, we describe the case of pancytopenic and transfusion-dependent twin brothers at our center whose bone marrow puncture revealed low bone marrow hyperplasia. Whole-exome sequencing revealed that the twins had a new germline GATA1 mutation (nm_002049: exon 3:c.515 T >C:p.F172S), which confirmed the diagnosis of GATA1 mutation-related pancytopenia. The mutation was inherited from their mother, who was heterozygous for the mutation. Sanger sequencing verified the pathogenicity of the mutation. Further family morbidity survey confirmed that GATA1 mutation-related pancytopenia is an X-linked recessive genetic disorder. We developed haploid hematopoietic stem cell transplantation programs for twins, with the father as the only donor, and finally, the hematopoietic reconstruction was successful. Although they experienced acute graft-versus-host disease, hemorrhagic cystitis, and a viral infection in the early stage, no abnormal manifestations or transplant-related complications were observed 3 months after transplantation. Through hematopoietic stem cell transplantation technology for one donor and two receptors, we eventually cured the twins. The p.F172S variant in the new germline GATA1 mutation may play an essential role in the pathogenesis of GATA1 mutation-related cytopenia.
由于 GATA1 异常调节导致的细胞减少症可能表现为不同程度的血小板减少症和/或贫血,且在男童中比在女童中更为严重。在这里,我们描述了一对在我们中心接受治疗的全血细胞减少症和依赖输血的双胞胎兄弟的病例,他们的骨髓穿刺显示骨髓增生低下。全外显子组测序显示,这对双胞胎携带一种新的种系 GATA1 突变(nm_002049:exon 3:c.515 T>C:p.F172S),证实了 GATA1 突变相关全血细胞减少症的诊断。该突变是从他们的母亲那里遗传来的,母亲是该突变的杂合子。Sanger 测序证实了突变的致病性。进一步的家族发病情况调查证实,GATA1 突变相关全血细胞减少症是一种 X 连锁隐性遗传疾病。我们为双胞胎制定了单倍体造血干细胞移植方案,仅父亲作为供体,最终造血重建成功。尽管他们在早期经历了急性移植物抗宿主病、出血性膀胱炎和病毒感染,但在移植后 3 个月没有观察到异常表现或与移植相关的并发症。通过一个供体和两个受体的造血干细胞移植技术,我们最终治愈了这对双胞胎。新种系 GATA1 突变中的 p.F172S 变异可能在 GATA1 突变相关细胞减少症的发病机制中发挥重要作用。