TREX-1-Related Disease Associated with the Presence of Cryofibrinogenemia

Paradis, Catherine; Cadieux-Dion, Maxime; Meloche, Catherine; Gravel, Mathieu; Paradis, Jean; Roches, Anne Des; Leclerc, Gilles; Cossette, Patrick; Bégin, Philippe

doi:10.1007/s10875-018-0584-x

Cited by 7 publications

(6 citation statements)

References 29 publications

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“…Our experience with this study might suggest that CF should also be evaluated in idiopathic chilblains and in those associated with autoinflammatory disorders, such as type 1 interferonopathies, as well as monogenic familiar chilblain lupus 38 . Indeed, there is one report regarding CF and familiar chilblain lupus as a result of mutation on the TREX gene 39 . If confirmed in these scenarios, in which interferon type 1 is elevated, CF secondary to infection could be hypothetically explained by an elevated interferon response to infection in susceptible patients.…”

Section: Discussionmentioning

confidence: 89%

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High prevalence of cryofibrinogenemia in patients with chilblains during the COVID‐19 outbreak

et al. 2020

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Background Many cutaneous manifestations have been described in possible association with the COVID-19 pandemic, including acral lesions resembling chilblains. The underlying pathomechanisms of COVID-19 chilblains are not fully understood. The aim of this study was to describe the clinical, pathological, and laboratory findings of a series of patients who developed chilblains during the COVID-19 outbreak and to investigate the possible factors that could be involved in the pathogenesis of these lesions. Methods We conducted a prospective cohort study that included 54 patients who presented with chilblains during the highest peak in the incidence of COVID-19 in Cantabria (northern Spain). Skin biopsies were performed on 10 of these patients who presented with recent lesions. Laboratory investigations, including immunological analysis, serological studies, and the assessment of cryoproteins, were also performed. Results Most patients presented erythematous plaques located on the toes and/or purpuric macules located on the feet. Histopathological findings were compatible with those of idiopathic chilblains. Immunohistochemical evaluation showed C3d and C4d deposits in the vessel walls in seven cases. The autoimmunity panel was negative in most of our series. Cryoprotein testing showed positive cryofibrinogen in two-thirds (66.7%) of the patients assessed. On follow-up, most patients presented almost complete resolution, although six patients required prednisone and antiaggregant drug treatment. Conclusions This study shows, for the first time to our knowledge, a high prevalence of cryofibrinogenemia in patients with chilblains during the COVID-19 pandemic. Cryofibrinogenemia could be implicated in the pathogenesis of chilblains related to COVID-19.

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Section: Discussionmentioning

confidence: 89%

“…38 Indeed, there is one report regarding CF and familiar chilblain lupus as a result of mutation on the TREX gene. 39 If confirmed in these scenarios, in which interferon type 1 is elevated, CF secondary to infection could be hypothetically explained by an elevated interferon response to infection in susceptible patients.…”

Section: Discussionmentioning

confidence: 96%

High prevalence of cryofibrinogenemia in patients with chilblains during the COVID‐19 outbreak

et al. 2020

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“…The gene responsible for RVCL-S is TREX1 and it encodes the TREX1 protein, which, after mutation, makes endothelial cells more vulnerable to oxidative DNA damage [ 31 ]. TREX1 is detectable in the microglia surrounding the white matter micro vascularization, and probably the incorrect localization of TREX1 may induce the vulnerability to white matter failure [ 32 , 33 ]. It has been reported that these circulating endothelial markers are present in retinal vasculopathy with cerebral leukoencephalopathy [ 34 , 35 ].…”

Section: Resultsmentioning

confidence: 99%

Stroke and Etiopathogenesis: What Is Known?

Ciarambino,

Crispino,

Mastrolorenzo

et al. 2022

Genes

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Background: A substantial portion of stroke risk remains unexplained, and a contribution from genetic factors is supported by recent findings. In most cases, genetic risk factors contribute to stroke risk as part of a multifactorial predisposition. A major challenge in identifying the genetic determinants of stroke is fully understanding the complexity of the phenotype. Aims: Our narrative review is needed to improve our understanding of the biological pathways underlying the disease and, through this understanding, to accelerate the identification of new drug targets. Methods: We report, the research in the literature until February 2022 in this narrative review. The keywords are stroke, causes, etiopathogenesis, genetic, epigenetic, ischemic stroke. Results: While better risk prediction also remains a long-term goal, its implementation is still complex given the small effect-size of genetic risk variants. Some authors encourage the use of stroke genetic panels for stroke risk assessment and further stroke research. In addition, new biomarkers for the genetic causes of stroke and new targets for gene therapy are on the horizon. Conclusion: We summarize the latest evidence and perspectives of ischemic stroke genetics that may be of interest to the physician and useful for day-to-day clinical work in terms of both prevention and treatment of ischemic stroke.

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“…Muted TREX1 protein maintains DNase activity, but aberrant localization of muted protein due to impaired translocation into the nucleus in response to oxidative DNA damage may be associated with systemic micro-vascular endotheliopathy in patients with RVCL. Malfunctioning of TREX1 is associated with a broad spectrum of inflammatory and autoimmune diseases which are apparently independent, such as Aicardi-Goutieres syndrome (AGS), cryofibrinogenemia, familial chilblain lupus (FCL), systemic lupus erythematosus (SLE) and retinal vasculopathy with cerebral leukodystrophy (RVCL) [ 17 , 19 , 20 , 21 , 22 ].…”

Section: Resultsmentioning

confidence: 99%

Monogenic Causes of Strokes

Chojdak-Łukasiewicz¹,

Dziadkowiak²,

Budrewićz³

2021

Genes

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Strokes are the main cause of death and long-term disability worldwide. A stroke is a heterogeneous multi-factorial condition, caused by a combination of environmental and genetic factors. Monogenic disorders account for about 1% to 5% of all stroke cases. The most common single-gene diseases connected with strokes are cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) Fabry disease, mitochondrial myopathy, encephalopathy, lactacidosis, and stroke (MELAS) and a lot of single-gene diseases associated particularly with cerebral small-vessel disease, such as COL4A1 syndrome, cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), and Hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS). In this article the clinical phenotype for the most important single-gene disorders associated with strokes are presented. The monogenic causes of a stroke are rare, but early diagnosis is important in order to provide appropriate therapy when available.

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TREX-1-Related Disease Associated with the Presence of Cryofibrinogenemia

Cited by 7 publications

References 29 publications

High prevalence of cryofibrinogenemia in patients with chilblains during the COVID‐19 outbreak

High prevalence of cryofibrinogenemia in patients with chilblains during the COVID‐19 outbreak

Stroke and Etiopathogenesis: What Is Known?

Monogenic Causes of Strokes

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