P249 Recurrent episodes of acute necrotizing encephalopathy caused by a mutation in a component of the nuclear pore, RANBP2

2009 ◽  
Vol 13 ◽  
pp. S98-S99
Author(s):  
S. Mastroyianni ◽  
A. Skardoutsou ◽  
K. Voudris ◽  
E. Katsarou ◽  
J. Nikas ◽  
...  
2019 ◽  
Author(s):  
Qingtang Shen ◽  
Yifan E. Wang ◽  
Mathew Truong ◽  
Kohila Mahadevan ◽  
Jing Ze Wu ◽  
...  

SUMMARYRanBP2/Nup358 is one of the main components of the cytoplasmic filaments of the nuclear pore complex. It has been speculated that RanBP2, which has an E3 SUMO-ligase domain, may alter the composition of messenger ribonucleoprotein (mRNP) complexes as they emerge from the nuclear pore and thus regulate the ultimate fate of the mRNA in the cytoplasm. Four separate missense mutations in RanBP2 cause Acute Necrotizing Encephalopathy 1 (ANE1), which manifests as a sharp rise in cytokine production after common viral infections such as influenza and parainfluenza. However, how RanBP2 and its ANE1-associated mutations affect cytokine production is not well understood. Here we report that RanBP2 represses the translation of the interleukin-6 (IL6) mRNA, which encodes a cytokine that is aberrantly up-regulated in ANE1. Our data indicates that soon after its production, the IL6 mRNP recruits the RNA-induced silencing complex (RISC) bound to Let7 miRNA. After this mRNP is exported, RanBP2 sumoylates the RISC-component AGO1, thereby stabilizing it and enforcing mRNA silencing. Collectively, these results support a model whereby RanBP2 promotes an mRNP remodelling event that is critical for the miRNA-mediated suppression of clinically relevant mRNAs, such as IL6.


2009 ◽  
Vol 84 (1) ◽  
pp. 44-51 ◽  
Author(s):  
Derek E. Neilson ◽  
Mark D. Adams ◽  
Caitlin M.D. Orr ◽  
Deborah K. Schelling ◽  
Robert M. Eiben ◽  
...  

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Xiujuan Wu ◽  
Wei Wu ◽  
Wei Pan ◽  
Limin Wu ◽  
Kangding Liu ◽  
...  

Acute necrotizing encephalopathy (ANE) is a rare but distinctive type of acute encephalopathy with global distribution. Occurrence of ANE is usually preceded by a virus-associated febrile illness and ensued by rapid deterioration. However, the causal relationship between viral infections and ANE and the exact pathogenesis of ANE remain unclear; both environmental and host factors might be involved. Most cases of ANE are sporadic and nonrecurrent, namely, isolated or sporadic ANE; however, few cases are recurrent and with familial episodes. The recurrent and familial forms of ANE were found to be incompletely autosomal-dominant. Further the missense mutations in the gene encoding the nuclear pore protein Ran Binding Protein 2 (RANBP2) were identified. Although the clinical course and the prognosis of ANE are diverse, the hallmark of neuroradiologic manifestation of ANE is multifocal symmetric brain lesions which are demonstrated by computed tomography (CT) or magnetic resonance imaging (MRI). The treatment of ANE is still under investigation. We summarize the up-to-date knowledge on ANE, with emphasis on prompt diagnosis and better treatment of this rare but fatal disease.


PLoS Genetics ◽  
2021 ◽  
Vol 17 (2) ◽  
pp. e1009378
Author(s):  
Qingtang Shen ◽  
Yifan E. Wang ◽  
Mathew Truong ◽  
Kohila Mahadevan ◽  
Jingze J. Wu ◽  
...  

Mutations in RanBP2 (also known as Nup358), one of the main components of the cytoplasmic filaments of the nuclear pore complex, contribute to the overproduction of acute necrotizing encephalopathy (ANE1)-associated cytokines. Here we report that RanBP2 represses the translation of the interleukin 6 (IL6) mRNA, which encodes a cytokine that is aberrantly up-regulated in ANE1. Our data indicates that soon after its production, the IL6 messenger ribonucleoprotein (mRNP) recruits Argonautes bound to let-7 microRNA. After this mRNP is exported to the cytosol, RanBP2 sumoylates mRNP-associated Argonautes, thereby stabilizing them and enforcing mRNA silencing. Collectively, these results support a model whereby RanBP2 promotes an mRNP remodelling event that is critical for the miRNA-mediated suppression of clinically relevant mRNAs, such as IL6.


2021 ◽  
pp. 194187442199137
Author(s):  
Yan Wang ◽  
John R. Younce ◽  
Joel S. Perlmutter ◽  
Soe S. Mar

Acute necrotizing encephalopathy (ANE) is a rare para-infectious encephalopathy that classically occurs in children. However, ANE should be considered in the differential diagnosis of adults with symmetric brain lesions after a prodromal illness given recent reports of coronavirus disease of 2019 (COVID-19) to presumably cause ANE in adults. We report a case of a 29-year-old male presenting with fever, malaise, and rapid deterioration into coma. Brain magnetic resonance imaging revealed multifocal symmetric areas of diffusion restriction and surrounding vasogenic edema involving bilateral thalami, pons and cerebellar hemispheres with a core of susceptibility artifact, and minimal thalamic contrast enhancement, most consistent with ANE. Extensive infectious workup revealed isolated Escherichia coli and Neisseria gonorrhoeae in his urine. Despite the severe encephalopathy on initial presentation, the patient improved with intravenous antibiotics and supportive management with minimal residual deficits at 9 months follow-up. We aim to provide an overview of the radiological features, differential diagnosis, treatment and prognosis of ANE. Becoming familiarized with this rare but devastating disease will improve detection, treatment, and ultimately prognosis, especially in the era of a new pandemic.


2018 ◽  
Vol 40 (3) ◽  
pp. 639-641 ◽  
Author(s):  
Vedran Stevanović ◽  
Zoran Barušić ◽  
Klaudija Višković ◽  
Oktavija Đaković Rode ◽  
Goran Tešović

2011 ◽  
Vol 45 (5) ◽  
pp. 344-346 ◽  
Author(s):  
Akira Kumakura ◽  
Chihiro Iida ◽  
Makiko Saito ◽  
Masashi Mizuguchi ◽  
Daisuke Hata

2019 ◽  
Vol 29 (07) ◽  
pp. 649-653 ◽  
Author(s):  
Farida Jan ◽  
Sidra Jafri ◽  
Shahnaz Ibrahim

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