Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Medical Sciences, Nagasaki, Japan.
Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Medical Sciences, Nagasaki, Japan.
Clin Immunol. 2021 Jun;227:108732. doi: 10.1016/j.clim.2021.108732. Epub 2021 Apr 21.
The 3' repair exonuclease 1 (TREX1) gene encodes a nuclear protein with 3' exonuclease activity, and the mutations have been associated with autoimmune diseases. Herein, we performed genetic analysis for the TREX1 gene in 55 patients with systemic lupus erythematosus (SLE). We identified one SLE patient with overlapping dermatomyositis having a heterozygous p.Asp130Asn mutation in the TREX1 gene. The patient had a high level of serum interferon (IFN)-α compared with that in healthy controls and other patients with SLE. In addition, the patient expressed elevated IFN signature genes compared with healthy controls. Our molecular dynamics simulation of the TREX1 protein in a complex with double-stranded DNA revealed that the D130N mutant causes significant changes in the active site's interaction network. One of our cases exhibited a heterozygous TREX1 p.Asp130Asn mutation that contributed to the type I IFN pathway, which may lead to the development of a severe SLE phenotype.
3' 修复外切核酸酶 1（TREX1）基因编码一种具有 3' 外切核酸酶活性的核蛋白，其突变与自身免疫性疾病有关。在此，我们对 55 例系统性红斑狼疮（SLE）患者的 TREX1 基因进行了遗传分析。我们在 1 例重叠皮肌炎的 SLE 患者中发现 TREX1 基因杂合 p.Asp130Asn 突变。与健康对照者和其他 SLE 患者相比，该患者血清干扰素（IFN）-α水平较高。此外，与健康对照者相比，该患者表达的 IFN 特征基因升高。我们对 TREX1 蛋白与双链 DNA 复合物的分子动力学模拟表明，D130N 突变导致活性位点相互作用网络发生显著变化。我们的一个病例表现出 TREX1 p.Asp130Asn 杂合突变，该突变导致 I 型 IFN 通路的激活，可能导致严重的 SLE 表型的发展。
