TREX1 plays multiple roles in human diseases

Wang, Qing; Du, Juan; Hua, Shucheng; Zhao, Ke

doi:10.1016/j.cellimm.2022.104527

Cited by 4 publications

(3 citation statements)

References 130 publications

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“…The TREX1 gene is located at chromosome 3p21 and encodes three-prime repair exonuclease 1, which is an essential exonuclease in mammalian cells, and numerous in vivo and in vitro data have shown its participation in immune regulation and genotoxicity remediation [ 32 ]. Mutations in TREX1 lead to protein inactivation, resulting in excess interferon-1, leading to autoimmune disease.…”

Section: Discussionmentioning

confidence: 99%

A case of Aicardi-Goutières syndrome caused by TREX1 gene mutation

Zheng

Shao

Ding

et al. 2023

BMC Pregnancy Childbirth

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Aicardi-Goutières syndrome (AGS) is a rare genetic disorder involving the central nervous system and autoimmune abnormalities, leading to severe intellectual and physical disability with poor prognosis. AGS has a phenotype similar to intrauterine viral infection, which often leads to delays in genetic counseling. In this study, we report a case with a prenatal diagnosis of AGS. The first fetal ultrasound detected bilateral lateral ventricle cystic structures, and fetal MRI was performed to identify other signs. The right parietal lobe signal showed cerebral white matter abnormalities, and fetal brain development level was lower than that of normal fetuses of the same gestational age. Whole-exome sequencing revealed that the fetus carried the TREX1:NM_033629.6:exon2:c.294dup:p. C99Mfs*3 variant, suggesting that the c.294dup mutation of the TREX1 gene was the pathogenic mutation site, and the final comprehensive diagnosis was AGS1. In this article, we also reviewed the previous literature for possible phenotypes in the fetus and found that microcephaly and intrauterine growth retardation may be the first and most important markers of the intrauterine phenotype of AGS.

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Section: Discussionmentioning

confidence: 99%

A case of Aicardi-Goutières syndrome caused by TREX1 gene mutation

Zheng

Shao

Ding

et al. 2023

BMC Pregnancy Childbirth

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“…46 TREX1 mutants with no exonuclease activity result in accumulated DNAs in the cytoplasm that trigger overexpression of type I IFNs through the cGAS-STING T A B L E 1 AGS-related genes and functions of their expression products. pathway, thereby causing AGS 47 (Figure 1). It has been known that most TREX1-associated AGS are autosomal recessive while a few cases of TREX1 variants cause dominant AGS 48 (Table 1).…”

Section: Trex1mentioning

confidence: 99%

“…The C‐terminal transmembrane domain is responsible for anchoring TREX1 to the endoplasmic reticulum, while the exonuclease domain remains in the cytoplasm 46 . TREX1 mutants with no exonuclease activity result in accumulated DNAs in the cytoplasm that trigger overexpression of type I IFNs through the cGAS‐STING pathway, thereby causing AGS 47 (Figure 1). It has been known that most TREX1‐associated AGS are autosomal recessive while a few cases of TREX1 variants cause dominant AGS 48 (Table 1).…”

Section: Pathogenic Genesmentioning

confidence: 99%

Aicardi–Goutières syndrome: A monogenic type I interferonopathy

Liu

Shi

2023

Scand J Immunol

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Aicardi–Goutières syndrome (AGS) is a rare monogenic autoimmune disease that primarily affects the brains of children patients. Its main clinical features include encephalatrophy, basal ganglia calcification, leukoencephalopathy, lymphocytosis and increased interferon‐α (IFN‐α) levels in the patient's cerebrospinal fluid (CSF) and serum. AGS may be caused by mutations in any one of nine genes (TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, IFIH1, LSM11 and RNU7‐1) that result in accumulation of self‐nucleic acids in the cytoplasm or aberrant sensing of self‐nucleic acids. This triggers overproduction of type I interferons (IFNs) and subsequently causes AGS, the prototype of type I interferonopathies. This review describes the discovery history of AGS with various genotypes and provides the latest knowledge of clinical manifestations and causative genes of AGS. The relationship between AGS and type I interferonopathy and potential therapeutic methods for AGS are also discussed in this review.

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