Retinal Vasculopathy With Cerebral Leukodystrophy: Clinicopathologic Features of an Autopsied Patient With a Heterozygous TREX 1 Mutation.

Abstract:

:Retinal vasculopathy with cerebral leukodystrophy (RVCL) is an autosomal-dominant disorder involving the cerebral, retinal, renal, and other systemic microvessels due to frameshift mutations in the TREX1 gene. Under physiological conditions, the TREX1 protein is localized in the cellular cytoplasm and perinuclear area, but translocates into the nucleus in response to oxidative DNA damage. It has been speculated that aberrant localization of the protein may be associated with systemic microangiopathy in patients with RVCL. However, cellular expression of TREX1 in the brain and visceral organs of patients with RVCL has been unclear. Here, we report the clinicopathologic features of an autopsied patient with a heterozygous T249fs mutation in TREX1. The patient showed the clinical phenotype of vasculopathy with retinopathy, nephropathy, and stroke. CT with contrast enhancement demonstrated a tumorous lesion in the subcortical white matter. Histologically, the lesion consisted of confluent foci of necrosis with calcification and fibrous thickening of small vessel walls. TREX1 immunohistochemistry demonstrated positivity in the nuclei of cells in the CNS and visceral organs, indicating aberrant localization of the truncated protein, and the expression was remarkable in oligodendrocytes within the lesion, suggesting possible involvement of the protein in the pathomechanism of vasculopathy leading to white matter degeneration.

authors

Saito R,Nozaki H,Kato T,Toyoshima Y,Tanaka H,Tsubata Y,Morioka T,Horikawa Y,Oyanagi K,Morita T,Onodera O,Kakita A

doi

10.1093/jnen/nly115

subject

Has Abstract

pub_date

2019-02-01 00:00:00

pages

181-186

issue

2

eissn

0022-3069

issn

1554-6578

pii

5250740

journal_volume

78

pub_type

杂志文章
  • Pathological Relationship Between Adamantinomatous Craniopharyngioma and Adjacent Structures Based on QST Classification.

    abstract::The aim of this study was to clarify pathological and anatomical relationships between adamantinomatous craniopharyngiomas (ACP) and their surrounding structures. We previously established a QST classification scheme based on the apparent anatomic origin of the tumors. According to this classification, 13 type Q tumor...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/nly083

    authors: Liu Y,Qi ST,Wang CH,Pan J,Fan J,Peng JX,Zhang X,Bao Y,Liu YW

    更新日期:2018-11-01 00:00:00

  • Characterization of ubiquitinated intraneuronal inclusions in a novel Belgian frontotemporal lobar degeneration family.

    abstract::The most common histologic feature in patients with frontotemporal lobar degeneration (FTLD) is intracellular brain inclusions of yet uncharacterized proteins that react with antiubiquitin (Ub) antibodies, but not with tau or synuclein (FTLD-U). We identified a four-generation Belgian FTLD family in which 8 patients h...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/01.jnen.0000205147.39210.c7

    authors: Pirici D,Vandenberghe R,Rademakers R,Dermaut B,Cruts M,Vennekens K,Cuijt I,Lübke U,Ceuterick C,Martin JJ,Van Broeckhoven C,Kumar-Singh S

    更新日期:2006-03-01 00:00:00

  • Cytokines and Mycobacterium leprae induce apoptosis in human Schwann cells.

    abstract::The development of deformities during the course of leprosy disease is a major public health concern worldwide. It is possible that cytokine production and apoptosis of Schwann cells (SCs) directly affect nerve degeneration and regeneration leading to injury of the myelin sheath and axon. In the present study, the exp...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/01.jnen.0000182982.09978.66

    authors: Oliveira RB,Sampaio EP,Aarestrup F,Teles RM,Silva TP,Oliveira AL,Antas PR,Sarno EN

    更新日期:2005-10-01 00:00:00

  • Fibroblasts can express glial fibrillary acidic protein (GFAP) in vivo.

    abstract::Neuropathologists use anti-glial fibrillary acidic protein (GFAP) antibodies as specific markers for glial cells, and neurobiologists use GFAP for targeting transgenes to glial cells. Since GFAP has also been detected in non-glial cells, we systematically analyzed GFAP expression in human and murine non-CNS tissues us...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/60.5.449

    authors: Hainfellner JA,Voigtländer T,Ströbel T,Mazal PR,Maddalena AS,Aguzzi A,Budka H

    更新日期:2001-05-01 00:00:00

  • Traumatically induced reactive change as visualized through the use of monoclonal antibodies targeted to neurofilament subunits.

    abstract::Reactive axonal change has long been recognized as a feature of traumatic brain injury. To date, the histological methods used to identify reactive axons have been of limited utility, and they have not provided insight into the initial intraaxonal event that triggers reactive change. In this investigation, monoclonal ...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199203000-00006

    authors: Yaghmai A,Povlishock J

    更新日期:1992-03-01 00:00:00

  • Macrophage properties during peripheral nervous tissue rejection in vitro.

    abstract::The present study introduces an in vitro model of xenogeneic peripheral nerve rejection to analyze the role of macrophages in this complex immunological situation. Nerve-sensitized mouse peritoneal exudate cells were co-cultured with rat peripheral nerve segments. The cultured rat nerve segments were fulminantly rejec...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199401000-00007

    authors: Brück W,Brück Y,Maruschak B,Friede RL

    更新日期:1994-01-01 00:00:00

  • Lewy body pathology in normal elderly subjects.

    abstract::Lewy bodies and Lewy neurites are the hallmark neuropathologic findings in Parkinson disease, Parkinson disease with dementia, dementia with Lewy bodies, and other alpha-synucleinopathies. They have also been described in the brains of normal older individuals and referred to as incidental Lewy body disease. The purpo...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e3181ac10a7

    authors: Markesbery WR,Jicha GA,Liu H,Schmitt FA

    更新日期:2009-07-01 00:00:00

  • Identification of novel biomarkers in pediatric primitive neuroectodermal tumors and ependymomas by proteome-wide analysis.

    abstract::The aim of this study was to identify aberrantly expressed proteins in pediatric primitive neuroectodermal tumors (PNETs) and ependymomas. Tumor tissue of 29 PNET and 12 ependymoma patients was subjected to 2-dimensional difference gel electrophoresis. Gel analysis resulted in 79 protein spots being differentially exp...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/01.jnen.0000240475.35414.c3

    authors: de Bont JM,den Boer ML,Kros JM,Passier MM,Reddingius RE,Smitt PA,Luider TM,Pieters R

    更新日期:2007-06-01 00:00:00

  • Comparative Ultrastructural and Stereological Analyses of Unruptured and Ruptured Saccular Intracranial Aneurysms.

    abstract::Insight into processes leading to rupture of intracranial aneurysms (IAs) may identify biomarkers for rupture or lead to management strategies reducing the risk of rupture. We characterized and quantified (ultra)structural differences between unruptured and ruptured aneurysmal walls. Six unruptured and 6 ruptured IA f...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/nlx075

    authors: Korkmaz E,Kleinloog R,Verweij BH,Allijn IE,Hekking LHP,Regli L,Rinkel GJE,Ruigrok YM,Andries Post J

    更新日期:2017-10-01 00:00:00

  • Comparative genomic hybridization in central and peripheral nervous system tumors of childhood and adolescence.

    abstract::Brain tumors amount to less than 2% of all malignant neoplasms. However, they account for approximately 20% of all childhood cancers and are the leading cause of cancer mortality among children. Recently, enormous progress has been achieved in the field of pediatric neuro-oncology regarding the classification of child...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章,评审

    doi:10.1093/jnen/63.5.399

    authors: Rickert CH,Paulus W

    更新日期:2004-05-01 00:00:00

  • The life and death of oligodendrocytes in vanishing white matter disease.

    abstract::Vanishing white matter disease (VWM) is a progressive cavitating disease of central white matter due to a deficiency of the translation initiation factor eIF2B. Oligodendrocytes appear to be numerically increased in some white matter areas, while decreased in others. We compared oligodendrocytes of cerebral, cerebella...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/63.6.618

    authors: Van Haren K,van der Voorn JP,Peterson DR,van der Knaap MS,Powers JM

    更新日期:2004-06-01 00:00:00

  • Tissue microarrays in the study of non-neoplastic disease of the nervous system.

    abstract::Tissue microarrays (TMAs), also known as "tissue chips," are a recently developed method that allows small cores or discs of tissue from dozens or hundreds of (usually paraffin-embedded) specimens to be re-embedded in a tissue block, which can then be further sectioned. The tissue cores can subsequently be studied usi...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章,评审

    doi:10.1093/jnen/61.8.653

    authors: Goldstine J,Seligson DB,Beizai P,Miyata H,Vinters HV

    更新日期:2002-08-01 00:00:00

  • Prognostic limitations of the Daumas-Duport grading scheme in childhood supratentorial astroglial tumors.

    abstract::The Daumas-Duport grading scheme (DDGS) is a commonly used method for determining the grade of a tumor. It scores 4 histologic features and is used as a prognostic tool in adult astroglial tumors. This system of assigning children to prognostically homogeneous groups has not been evaluated. The Childhood Brain Tumor C...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199811000-00006

    authors: Brown WD,Gilles FH,Tavaré CJ,Rorke LB,Davis RL,Adelman L,Hedley-Whyte ET,Leviton A

    更新日期:1998-11-01 00:00:00

  • Histopathologic Analysis of Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CARASIL): A Report of a New Genetically Confirmed Case and Comparison to 2 Previous Cases.

    abstract::Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a nonhypertensive hereditary cerebral small vessel disease that is caused by mutations in a single gene, HTRA1. The HTRA1 protein normally represses transforming growth factor-β (TGF-β) signaling and its mutations ...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/nlw078

    authors: Ito S,Takao M,Fukutake T,Hatsuta H,Funabe S,Ito N,Shimoe Y,Niki T,Nakano I,Fukayama M,Murayama S

    更新日期:2016-11-01 00:00:00

  • Laminin in rat sciatic nerve undergoing Wallerian degeneration. Immunofluorescence study with laminin and neurofilament antisera.

    abstract::Immunofluorescence with laminin antisera revealed a striking change in the localization of this basal membrane glycoprotein in rat sciatic nerve as a result of Wallerian degeneration. The staining was confined to the endoneurium in normal sciatic nerve and during the first days of degeneration. On day 11 endoneurial t...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-198401000-00008

    authors: Bignami A,Chi NH,Dahl D

    更新日期:1984-01-01 00:00:00

  • Distribution, levels, and activity of glycogen synthase kinase-3 in the Alzheimer disease brain.

    abstract::A number of studies have implicated a proline-directed protein kinase, glycogen synthase kinase-3 (GSK-3) in the hyperphosphorylation of tau in Alzheimer's disease (AD). Toward understanding the role of GSK-3 in the abnormal hyperphosphorylation of tau in AD we have found that GSK-3 is prominently present in neuronal ...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199701000-00007

    authors: Pei JJ,Tanaka T,Tung YC,Braak E,Iqbal K,Grundke-Iqbal I

    更新日期:1997-01-01 00:00:00

  • Meningoencephalitis and demyelination are pathologic manifestations of primary polyomavirus infection in immunosuppressed rhesus monkeys.

    abstract::The human polyomavirus JC (JCV) is the etiologic agent of progressive multifocal leukoencephalopathy (PML), a demyelinating disease of the CNS that occurs in immunosuppressed individuals. Because polyomavirus-induced CNS pathology usually occurs as a result of the reactivation of latent virus, little is known about th...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/63.7.750

    authors: Axthelm MK,Koralnik IJ,Dang X,Wüthrich C,Rohne D,Stillman IE,Letvin NL

    更新日期:2004-07-01 00:00:00

  • 1,25 Dihydroxyvitamin D3 exerts regional effects in the central nervous system during experimental allergic encephalomyelitis.

    abstract::1,25-dihydroxyvitamin D3 (1,25-D3) is already known to prevent clinical signs of experimental allergic encephalomyelitis when animals are treated during the immunization phase. In the present work we have evaluated the ability of 1,25-D3 to inhibit chronic relapsing experimental allergic encephalomylitis (EAE) of the ...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199608000-00006

    authors: Nataf S,Garcion E,Darcy F,Chabannes D,Muller JY,Brachet P

    更新日期:1996-08-01 00:00:00

  • Subcellular localization of peptidylarginine deiminase 2 and citrullinated proteins in brains of scrapie-infected mice: nuclear localization of PAD2 and membrane fraction-enriched citrullinated proteins.

    abstract::Peptidylarginine deiminase (PAD) and citrullinated proteins have emerged as key molecules in various human diseases, but detailed subcellular localizations of PAD2 and citrullinated proteins are poorly mapped in brain under normal and pathologic conditions. We performed subcellular fractionation and electron microscop...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e318207559e

    authors: Jang B,Shin HY,Choi JK,Nguyen du PT,Jeong BH,Ishigami A,Maruyama N,Carp RI,Kim YS,Choi EK

    更新日期:2011-02-01 00:00:00

  • Neuropathology in depth: the role of confocal microscopy.

    abstract::This review surveys the rapidly increasing applications of confocal microscopy in neuropathology and related areas of experimental neurology. The ability of this new instrument to "optically section" thick samples has opened up to microscopic examination a wide range of previously difficult specimens. The basic operat...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章,评审

    doi:

    authors: Murray JM

    更新日期:1992-09-01 00:00:00

  • Immunity to transplantable nitrosourea-induced neurogenic tumors. II. Immunoprophylaxis of tumors of the brain.

    abstract::An effective method was sought to immunize rats against the growth of intracerebrally (IC) injected T9 tumor, a gliosarcoma cell line. Rats which were immunized with either 10(6) T9 cells mixed with 0.14 mg C. parvum, or 10(7) irradiated T9 cells showed tumor immunity to intradermal (ID) transplantation. However, to o...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-198303000-00002

    authors: Kida Y,Cravioto H,Hochwald GM,Hochgeschwender U,Ransohoff J

    更新日期:1983-03-01 00:00:00

  • First report of Creutzfeldt-Jakob disease occurring in 2 siblings unexplained by PRNP mutation.

    abstract::Sibling concurrence of pathologically confirmed prion disease has only been reported in association with pathogenic mutation of the prion protein gene (PRNP). Here, we report 2 siblings with classic neuropathologic features of sporadic Creutzfeldt-Jakob disease unexplained by PRNP mutation or known risk factors for ia...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e318182f36e

    authors: Webb TE,Pal S,Siddique D,Heaney DC,Linehan JM,Wadsworth JD,Joiner S,Beck J,Wroe SJ,Stevenson V,Brandner S,Mead S,Collinge J

    更新日期:2008-09-01 00:00:00

  • Porphyrin-laser photodynamic induction of focal brain necrosis.

    abstract::A noninvasive photodynamic method has been developed to produce focal brain necrosis using porphyrin activated in vivo with laser light. After peripheral injection of the photosensitive porphyrin derivative, Photofrin I, mice were irradiated on the posterior lateral aspect of the head through the intact depilated scal...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-198909000-00005

    authors: Stroop WG,Battles EJ,Townsend JJ,Schaefer DC,Baringer JR,Straight RC

    更新日期:1989-09-01 00:00:00

  • Virus-induced obesity in mice: association with a hypothalamic lesion.

    abstract::In an earlier study we found that a substantial percentage of mice surviving infection with canine distemper virus (CDV) slowly developed a morbid obesity syndrome. In the present study we wished to explore the role of the virus in the development of this syndrome. The distribution of viral antigen(s) in brains of pre...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199201000-00012

    authors: Nagashima K,Zabriskie JB,Lyons MJ

    更新日期:1992-01-01 00:00:00

  • Pathology of experimental compression neuropathy producing hyperesthesia.

    abstract::An experimental neuropathy in rats produced by tying loosely constrictive ligatures around one sciatic nerve has recently been shown to produce pain-related behavior that follows a reproducible time course. In the present study, we assessed the degree of thermal hyperesthesia and examined the sciatic nerves by light a...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199305000-00006

    authors: Sommer C,Galbraith JA,Heckman HM,Myers RR

    更新日期:1993-05-01 00:00:00

  • Regional heterogeneity in the proliferative activity of human gliomas as measured by the Ki-67 labeling index.

    abstract::The effects of regional heterogeneity on the accuracy of histological grading of gliomas are well known, but little has been reported about its implications for other diagnostic modalities. This study investigated the relationships of regional heterogeneity in tumor proliferative activity, measured by Ki-67 labeling i...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199311000-00008

    authors: Coons SW,Johnson PC

    更新日期:1993-11-01 00:00:00

  • Therapy of a murine model of pediatric brain tumors using a herpes simplex virus type-1 ICP34.5 mutant and demonstration of viral replication within the CNS.

    abstract::To develop improved therapies for medulloblastoma, we studied the ability of a neuroattenuated HSV-1 ICP34.5 mutant (variant-1716) to replicate within and destory an authentic medulloblastoma cell line known as Med 283 (D283) using immunohistochemistry, in situ hybridization, and viral titrations. In vitro studies sho...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199612000-00010

    authors: Lasner TM,Kesari S,Brown SM,Lee VM,Fraser NW,Trojanowski JQ

    更新日期:1996-12-01 00:00:00

  • Neurodegeneration in mice resulting from loss of functional selenoprotein P or its receptor apolipoprotein E receptor 2.

    abstract::Selenoprotein P (Sepp1) is involved in selenium homeostasis. Mice with a deletion of Sepp1, replacement of it by the shortened form Sepp1(Delta240-361), or deletion of its receptor apolipoprotein E receptor 2 develop severe neurologic dysfunction when fed low-selenium diet. Because the brainstems of Sepp1(-/-) mice ha...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e318160f347

    authors: Valentine WM,Abel TW,Hill KE,Austin LM,Burk RF

    更新日期:2008-01-01 00:00:00

  • c-Jun, JNK/SAPK kinases and transcription factor NF-kappa B are selectively activated in astrocytes, but not motor neurons, in amyotrophic lateral sclerosis.

    abstract::There is increasing evidence that oxidative damage plays a major role in amyotrophic lateral sclerosis (ALS), but how it contributes to motor neuron degeneration and astrocytic gliosis, two pathologic hallmarks of the disease, is unknown. A few studies have suggested that ALS motor neurons die via apoptosis and show u...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199712000-00006

    authors: Migheli A,Piva R,Atzori C,Troost D,Schiffer D

    更新日期:1997-12-01 00:00:00

  • Concurrent inactivation of RB1 and TP53 pathways in anaplastic oligodendrogliomas.

    abstract::Oligodendrogliomas are characterized by frequent loss of heterozygosity (LOH) on chromosomes 1p and 19q, but additional genetic alterations are likely to be involved. In this study, we screened 28 oligodendrogliomas (WHO grade II) and 20 anaplastic oligodendrogliomas (WHO grade III) for alterations in the RB1/CDK4/p16...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/60.12.1181

    authors: Watanabe T,Yokoo H,Yokoo M,Yonekawa Y,Kleihues P,Ohgaki H

    更新日期:2001-12-01 00:00:00