Retinal vasculopathy with cerebral leukoencephalopathy carrying &lt;i&gt;TREX1&lt;/i&gt; mutation diagnosed by the intracranial calcification: a case report

Komaki, Ryouhei; Ueda, Takahiro; Tsuji, Yusuke; Miyawaki, Toko; Kusuhara, Sentaro; Hara, Shigeo; Toda, Tatsushi

doi:10.5692/clinicalneurol.cn-001096

Cited by 6 publications

(12 citation statements)

References 18 publications

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“…Renal involvement has been described in a case with a gain-of-function mutation in IFIH1 [9]. Renal dysfunction caused by thrombotic microangiopathy has been reported in a case with C-terminal frameshift mutation in TREX1 [10]. Renal biopsy in our patient revealed glomerular sclerosis and tubular injury without amyloidosis.…”

Section: Discussionsupporting

confidence: 47%

Systemic inflammation and chronic kidney disease in a patient due to the RNASEH2B defect

Xia

Yang

2020

Preprint

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Introduction: Aicardi-Goutières (AGS) is a rare immune dysregulated disease due to mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, or IFIH1. Clinical features include basal ganglia calcifications, white matter abnormalities, and cerebral atrophy. Severe systemic inflammation and chronic kidney disease (CKD) are extremely rare in AGS. Herein, we report a patient presenting with systemic inflammation and CKD to broaden the clinical phenotype spectrum of the RNASEH2B defect. Methods: All testing and molecular genetic analysis were performed after obtaining the informed consent of the parents. Demographic, clinical, and laboratory findings were abstracted from outpatient and inpatient encounters. Cerebral magnetic resonance imaging (MRI), computed tomography (CT) scans, and renal biopsy histopathology reports were reviewed and summarized. Whole exome sequencing (WES) was performed on peripheral blood cells. After exposure to cGAMP in vitro for 24 hours, mRNA expression of twelve IFN-stimulated cytokine genes in PBMCs was assessed. Serum cytokine levels were detected by Milliplex. Results: A 11-year-old girl presented with recurrent aseptic fever, arthritis, chilblains, failure to thrive, mild hearing loss, and neurological manifestations. Laboratory and immunologic findings demonstrated lymphopenia, low complement levels, positive autoantibodies, elevated levels of acute-phase reactants and inflammatory cytokines. Cerebral imaging showed cerebral atrophy, white matter abnormalities, and intracranial calcification. Renal biopsy showed glomerular sclerosis in three of fourteen glomeruli, infiltration of lymphocytes and other mononuclear cells. WES revealed a homozygous and heterozygous mutations in RNASEH2B . Over-expression of IFN-stimulated cytokine genes was observed, including IFI44, IFI27, IFIT1, IFIT2, IFIT3, ISG15, OAS1, and SIGLEC1. Conclusions: To date, only two cases with AGS have been reported to have renal disease. Here, we describe a patient with both homozygous and heterozygous variants in RNASEH2B, presenting with neurological manifestations, persistently systemic autoinflammation, and CKD. CKD has never been reported in patients with AGS due to the RNASEH2B defect .

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Section: Discussionsupporting

confidence: 47%

Systemic inflammation and chronic kidney disease in a patient due to the RNASEH2B defect

Xia

Yang

2020

Preprint

View full text Add to dashboard Cite

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“…Renal involvement has been described in a case with a gain-of-function mutation in IFIH1 [9]. Renal dysfunction caused by thrombotic microangiopathy has been reported in a case with C-terminal frame-shift mutation in TREX1 [10]. Renal biopsy in our patient revealed glomerular sclerosis and tubular injury without amyloidosis.…”

Section: Discussionmentioning

confidence: 47%

Systemic inflammation and chronic kidney disease in a patient due to the RNASEH2B defect

Xia

Yang

2021

Pediatr Rheumatol

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Introduction Aicardi-Goutières (AGS) is a rare immune dysregulated disease due to mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, or IFIH1. Clinical features include basal ganglia calcifications, white matter abnormalities, and cerebral atrophy. Severe systemic inflammation and chronic kidney disease (CKD) are extremely rare in AGS. Herein, we report a patient presenting with systemic inflammation and CKD to broaden the clinical phenotype spectrum of the RNASEH2B defect. Methods All testing and molecular genetic analysis were performed after obtaining the informed consent of the parents. Demographic, clinical, and laboratory findings were abstracted from outpatient and inpatient encounters. Cerebral magnetic resonance imaging (MRI), computed tomography (CT) scans, and renal biopsy histopathology reports were reviewed and summarized. Whole exome sequencing (WES) was performed on peripheral blood cells. After exposure to cGAMP in vitro for 24 h, mRNA expression of 12 IFN-stimulated cytokine genes in PBMCs was assessed. Serum cytokine levels were detected by Milliplex. Results A 11-year-old girl presented with recurrent aseptic fever, arthritis, chilblains, failure to thrive, mild hearing loss, and neurological manifestations. Laboratory and immunologic findings demonstrated lymphopenia, low complement levels, positive autoantibodies, elevated levels of acute-phase reactants and inflammatory cytokines. Cerebral imaging showed cerebral atrophy, white matter abnormalities, and intracranial calcification. Renal biopsy showed glomerular sclerosis in 3 of 14 glomeruli, infiltration of lymphocytes and other mononuclear cells. WES revealed a homozygous and heterozygous mutations in RNASEH2B. Over-expression of IFN-stimulated cytokine genes was observed, including IFI44, IFI27, IFIT1, IFIT2, IFIT3, ISG15, OAS1, and SIGLEC1. Conclusions To date, only two cases with AGS have been reported to have renal disease. Here, we describe a patient with both homozygous and heterozygous variants in RNASEH2B, presenting with neurological manifestations, persistently systemic autoinflammation, and CKD. CKD has never been reported in patients with AGS due to the RNASEH2B defect. Trial registration Not applicable; this was a retrospective study.

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“…Although the symptoms may stabilize, the prognosis of this condition is generally poor due to its progressive nature [ 14 ]. Moreover, the authors have seen no benefit with plasmapheresis, IV immunoglobulin, or chronic immunosuppression [ 15 ]. The efficacy of antiproliferative or biologic agents such as cyclophosphamide, azathioprine, and natalizumab is controversial.…”

Section: Discussionmentioning

confidence: 99%

Tumor-Like Brain Lesions Associated With Variants of Uncertain Significance Compared to Previous Studies: A Case Report

Santellán-Hernández¹,

Romero-Luna²,

Ramírez-Cruz³

et al. 2022

Cureus

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TREX1 is a gene that encodes an exonuclease on the C-terminal strand at the 3 ́ end for DNA repair. Multiple syndromes associated with the alteration of this gene have been described, focusing in this case on retinal vasculopathy with cerebral leukodystrophy (RVCL). We present the case of a 44-year-old female patient with a familial history of cerebral pseudotumors. At the time of diagnosis, the patient presented weakness in the lower limbs and dysesthesias of the right body at the beginning of the clinical picture, without visual alterations or retinal changes at fundus examination. A cranial magnetic resonance imaging (MRI) study showed a pseudotumoral lesion at the inferior frontal gyrus with a report of a choline peak in spectroscopy, ring enhancement in contrasted T1 sequence, and apparent central necrosis. A molecular study shows a mutation in c2136G>A, c.799dup, and c.5312A>G related to genes expressing PDE6A, TREX1, and VCAN proteins, respectively, mutations that have not been previously reported.

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Retinal vasculopathy with cerebral leukoencephalopathy carrying <i>TREX1</i> mutation diagnosed by the intracranial calcification: a case report

Cited by 6 publications

References 18 publications

Systemic inflammation and chronic kidney disease in a patient due to the RNASEH2B defect

Systemic inflammation and chronic kidney disease in a patient due to the RNASEH2B defect

Systemic inflammation and chronic kidney disease in a patient due to the RNASEH2B defect

Tumor-Like Brain Lesions Associated With Variants of Uncertain Significance Compared to Previous Studies: A Case Report

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