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Systemic lupus erythematosus overlapping dermatomyositis owing to a heterozygous TREX1 Asp130Asn missense mutation.
- Source :
-
Clinical immunology (Orlando, Fla.) [Clin Immunol] 2021 Jun; Vol. 227, pp. 108732. Date of Electronic Publication: 2021 Apr 21. - Publication Year :
- 2021
-
Abstract
- 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.<br /> (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Antigens, Surface genetics
DNA metabolism
DNA ultrastructure
Dermatomyositis metabolism
Dermatomyositis physiopathology
Exodeoxyribonucleases metabolism
Exodeoxyribonucleases ultrastructure
GPI-Linked Proteins genetics
Heterozygote
Humans
Interferon Type I
Interferon-alpha metabolism
Lupus Erythematosus, Systemic metabolism
Lupus Erythematosus, Systemic physiopathology
Male
Molecular Docking Simulation
Mutation, Missense
Myxovirus Resistance Proteins genetics
Phosphoproteins metabolism
Phosphoproteins ultrastructure
Transcriptome
Tumor Suppressor Proteins genetics
Dermatomyositis genetics
Exodeoxyribonucleases genetics
Lupus Erythematosus, Systemic genetics
Phosphoproteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1521-7035
- Volume :
- 227
- Database :
- MEDLINE
- Journal :
- Clinical immunology (Orlando, Fla.)
- Publication Type :
- Academic Journal
- Accession number :
- 33892200
- Full Text :
- https://doi.org/10.1016/j.clim.2021.108732