Vanishing white matter disease

Author(s):  
Orna Elroy-Stein ◽  
Raphael Schiffmann
2020 ◽  
Author(s):  
Matthew D. Keefe ◽  
Haille E. Soderholm ◽  
Hung-Yu Shih ◽  
Tamara J. Stevenson ◽  
Kathryn A. Glaittli ◽  
...  

AbstractVanishing White Matter disease (VWM) is a severe leukodystrophy of the central nervous system caused by mutations in subunits of the eukaryotic initiation factor 2B complex (eIF2B). Current models only partially recapitulate key disease features, and pathophysiology is poorly understood. Through development and validation of zebrafish (Danio rerio) models of VWM, we demonstrate that zebrafish eif2b mutants phenocopy VWM, including impaired somatic growth, early lethality, impaired myelination, loss of oligodendrocyte precursor cells, increased apoptosis in the CNS, and impaired motor swimming behavior. Expression of human EIF2B2 in the zebrafish eif2b2 mutant rescues lethality and CNS apoptosis, demonstrating conservation of function between zebrafish and human. In the mutants, intron 12 retention leads to expression of a truncated eif2b5 transcript. Expression of the truncated eif2b5 in wild-type larva impairs motor behavior and activates the ISR, suggesting that a feed-forward mechanism in VWM is a significant component of disease pathophysiology.


PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e46715 ◽  
Author(s):  
Yuval Cabilly ◽  
Mali Barbi ◽  
Michal Geva ◽  
Liraz Marom ◽  
David Chetrit ◽  
...  

2008 ◽  
Vol 110 (10) ◽  
pp. 1068-1071 ◽  
Author(s):  
Nathalie Damon-Perriere ◽  
Patrice Menegon ◽  
Anne Olivier ◽  
Odile Boespflug-Tanguy ◽  
Florence Niel ◽  
...  

2021 ◽  
Vol 429 ◽  
pp. 118270
Author(s):  
Giulia Galli ◽  
Eleonora Virgilio ◽  
Paola Naldi ◽  
Riccardo Fornaro ◽  
Domizia Vecchio ◽  
...  

2005 ◽  
Vol 51 (11) ◽  
pp. 2031-2042 ◽  
Author(s):  
Adeline Vanderver ◽  
Raphael Schiffmann ◽  
Margaret Timmons ◽  
Katherine A Kellersberger ◽  
Dan Fabris ◽  
...  

Abstract Background: A biomarker for the diagnosis of childhood-onset ataxia and central nervous system hypomyelination (CACH)/vanishing white matter disease (VWM) would have clinical utility and pathophysiologic significance. Methods: We used 2-dimensional gel electrophoresis/mass spectrometry to compare the cerebrospinal fluid proteome of patients with mutation-confirmed CACH/VWM with that of unaffected controls. We characterized selected spots by in-gel digestion, matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry, and nanospray Fourier transform mass spectrometry. Results: A specific transferrin spot pattern was detected in the CSF samples of the CACH/VWM group (n = 7), distinguishing them from the control group (n = 23) and revealing that patients with CACH/VWM have a deficiency of the asialo form of transferrin usually present in healthy cerebrospinal fluid. The glycopeptide structure, determined from isolated transferrin spots by use of in-gel digestion and extraction, was found to be consistent with earlier reports. Conclusions: The transferrin isoform abnormality in the cerebrospinal fluid of patients with CACH/VWM appears unique and is a potential clinical diagnostic biomarker. The rapid, efficient diagnosis of this disorder would have a significant impact on clinical studies exploring new strategies for the management and treatment of this disease.


Neurographics ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. 22-24
Author(s):  
K.M. Beavers ◽  
M.A. Flores ◽  
A.I. Dagli ◽  
S.A. Messina

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