期刊
CLINICAL IMMUNOLOGY
卷 227, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2021.108732
关键词
Systemic lupus erythematosus; TREX1 gene; Interferon; Molecular dynamics simulation
类别
资金
- Japan Society for the Promotion of Science (JSPS) KAKENHI [19K17888, 19K16058]
- Grants-in-Aid for Scientific Research [19K17888, 19K16058] Funding Source: KAKEN
In this study, a patient with systemic lupus erythematosus carrying a heterozygous p.Asp130Asn mutation in the TREX1 gene was identified, leading to elevated serum interferon levels and abnormal expression of IFN signature genes. Molecular dynamics simulation showed that this mutation caused significant changes in the active site of the TREX1 protein.
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)-alpha 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据