Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Department of Allergy and Clinical Immunology, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.
BMC Med Genet. 2019 Mar 21;20(1):45. doi: 10.1186/s12881-019-0784-0.
DNA double-strand breaks (DSBs) are among the most deleterious types of DNA damage. DSBs are repaired by homologous recombination or non-homologous end-joining (NHEJ). NHEJ, which is central to the process of V(D)J recombination is the principle pathway for DSB repair in higher eukaryotes. Mutations in NHEJ1 gene have been associated with severe combined immunodeficiency.
The patient was a 3.5-year-old girl, a product of consanguineous first-degree cousin marriage, who was homozygous for a nonsense mutation in NHEJ1 gene. She had initially presented with failure to thrive, proportional microcephaly as well as autoimmune hemolytic anemia (AIHA), which responded well to treatment with prednisolone. However, the patient was immunocompetent despite having this pathogenic mutation.
Herein, we report on a patient who was clinically immunocompetent despite having a pathogenic mutation in NHEJ1 gene. Our findings provided evidence for the importance of other end-joining auxiliary pathways that would function in maintaining genetic stability. Clinicians should therefore be aware that pathogenic mutations in NHEJ pathway are not necessarily associated with clinical immunodeficiency.
DNA 双链断裂（DSBs）是最具危害性的 DNA 损伤类型之一。DSBs 通过同源重组或非同源末端连接（NHEJ）修复。NHEJ 是 V(D)J 重组过程的核心，是高等真核生物 DSB 修复的主要途径。NHEJ1 基因突变与严重联合免疫缺陷有关。
患者为 3.5 岁女孩，为近亲一级表亲婚配所生，NHEJ1 基因纯合子发生无义突变。她最初表现为生长不良、比例性小头畸形以及自身免疫性溶血性贫血（AIHA），泼尼松龙治疗反应良好。然而，尽管存在这种致病性突变，患者仍具有免疫能力。
本研究报告了一名患者，尽管存在 NHEJ1 基因突变，但在临床上仍具有免疫能力。我们的研究结果为其他末端连接辅助途径在维持遗传稳定性方面的重要性提供了证据。因此，临床医生应注意到 NHEJ 途径的致病性突变不一定与临床免疫缺陷相关。
