Gert C Scheper

Summary

Affiliation: VU University Medical Center
Country: The Netherlands

Publications

  1. ncbi Glia-specific activation of all pathways of the unfolded protein response in vanishing white matter disease
    Barbara Van Kollenburg
    Department of Pediatrics Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
    J Neuropathol Exp Neurol 65:707-15. 2006
  2. pmc eIF2B-related disorders: antenatal onset and involvement of multiple organs
    Marjo S van der Knaap
    Department of Child Neurology, Free University Medical Center, Amsterdam, The Netherlands
    Am J Hum Genet 73:1199-207. 2003
  3. ncbi The unfolded protein response in vanishing white matter disease
    J Patrick van der Voorn
    Department of Pediatrics Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
    J Neuropathol Exp Neurol 64:770-5. 2005
  4. ncbi Defective translation initiation causes vanishing of cerebral white matter
    Gert C Scheper
    Department of Pediatrics, VU University Medical Center, 1081 HV Amsterdam, The Netherlands
    Trends Mol Med 12:159-66. 2006
  5. ncbi Megalencephalic leukoencephalopathy with subcortical cysts: an update and extended mutation analysis of MLC1
    P K Ilja Boor
    Department of Pediatrics Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
    Hum Mutat 27:505-12. 2006
  6. doi Analysis of CLCN2 as candidate gene for megalencephalic leukoencephalopathy with subcortical cysts
    Gert C Scheper
    Department of Pediatrics, VU University Medical Center, Amsterdam, The Netherlands
    Genet Test Mol Biomarkers 14:255-7. 2010
  7. ncbi Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation
    Gert C Scheper
    Department of Pediatrics and Child Neurology, Vrije University Medical Center, 1081 HV Amsterdam, The Netherlands
    Nat Genet 39:534-9. 2007
  8. ncbi Pathogenic mutations causing LBSL affect mitochondrial aspartyl-tRNA synthetase in diverse ways
    Laura van Berge
    Department of Child Neurology, VU University Medical Center, De Boelalaan 1117, 1081 HV Amsterdam, The Netherlands
    Biochem J 450:345-50. 2013
  9. doi Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation is associated with cell-type-dependent splicing of mtAspRS mRNA
    Laura van Berge
    Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
    Biochem J 441:955-62. 2012
  10. ncbi Regulation of protein synthesis in lymphoblasts from vanishing white matter patients
    Barbara Van Kollenburg
    Dept of Pediatrics Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
    Neurobiol Dis 21:496-504. 2006

Collaborators

Detail Information

Publications27

  1. ncbi Glia-specific activation of all pathways of the unfolded protein response in vanishing white matter disease
    Barbara Van Kollenburg
    Department of Pediatrics Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
    J Neuropathol Exp Neurol 65:707-15. 2006
    ..The selective involvement of these cells suggests that inappropriate UPR activation may play a key role in the pathophysiology of VWM...
  2. pmc eIF2B-related disorders: antenatal onset and involvement of multiple organs
    Marjo S van der Knaap
    Department of Child Neurology, Free University Medical Center, Amsterdam, The Netherlands
    Am J Hum Genet 73:1199-207. 2003
    ....
  3. ncbi The unfolded protein response in vanishing white matter disease
    J Patrick van der Voorn
    Department of Pediatrics Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
    J Neuropathol Exp Neurol 64:770-5. 2005
    ..We demonstrate activation of the UPR in glia of patients with VWM. Our findings may point to a possible explanation for the dysmorphic glia, the increased numbers of oligodendrocytes, and the apoptotic loss of oligodendrocytes in VWM...
  4. ncbi Defective translation initiation causes vanishing of cerebral white matter
    Gert C Scheper
    Department of Pediatrics, VU University Medical Center, 1081 HV Amsterdam, The Netherlands
    Trends Mol Med 12:159-66. 2006
    ..Here, we discuss the mechanisms that might be responsible for the selective involvement of the brain white matter in VWM. At present, VWM research is in need of an animal model to study disease mechanisms and therapeutic interventions...
  5. ncbi Megalencephalic leukoencephalopathy with subcortical cysts: an update and extended mutation analysis of MLC1
    P K Ilja Boor
    Department of Pediatrics Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
    Hum Mutat 27:505-12. 2006
    ..Therefore, we suggest extended mutation analysis for the MLC1 gene, if no mutations are found during standard analysis...
  6. doi Analysis of CLCN2 as candidate gene for megalencephalic leukoencephalopathy with subcortical cysts
    Gert C Scheper
    Department of Pediatrics, VU University Medical Center, Amsterdam, The Netherlands
    Genet Test Mol Biomarkers 14:255-7. 2010
    ..Further, in electrophysiological experiments, one of the observed amino acid changes was shown to have no effect on the ClC-2-mediated currents. In conclusion, we found no evidence suggesting that the CLCN2 gene is involved in MLC...
  7. ncbi Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation
    Gert C Scheper
    Department of Pediatrics and Child Neurology, Vrije University Medical Center, 1081 HV Amsterdam, The Netherlands
    Nat Genet 39:534-9. 2007
    ..Enzyme activities of mutant proteins were decreased. We were surprised to find that activities of mitochondrial complexes from fibroblasts and lymphoblasts derived from affected individuals were normal, as determined by different assays...
  8. ncbi Pathogenic mutations causing LBSL affect mitochondrial aspartyl-tRNA synthetase in diverse ways
    Laura van Berge
    Department of Child Neurology, VU University Medical Center, De Boelalaan 1117, 1081 HV Amsterdam, The Netherlands
    Biochem J 450:345-50. 2013
    ..Most mutations have a clear impact on at least one of the properties of mtAspRS studied, probably resulting in a small contribution of the missense variants to the mitochondrial aspartylation activity in the cell...
  9. doi Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation is associated with cell-type-dependent splicing of mtAspRS mRNA
    Laura van Berge
    Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
    Biochem J 441:955-62. 2012
    ..The combined result of these two effects may explain the selective vulnerability of specific white matter tracts in LBSL patients...
  10. ncbi Regulation of protein synthesis in lymphoblasts from vanishing white matter patients
    Barbara Van Kollenburg
    Dept of Pediatrics Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
    Neurobiol Dis 21:496-504. 2006
    ..These findings could form part of the explanation for the episodes of rapid and severe deterioration in VWM patients that are precipitated by febrile infections...
  11. ncbi Vanishing white matter disease: a review with focus on its genetics
    Jan C Pronk
    Department of Human Genetics, VU University Medical Center, Amsterdam, The Netherlands
    Ment Retard Dev Disabil Res Rev 12:123-8. 2006
    ..The pathophysiology of the disease is still poorly understood...
  12. pmc MLC1 is associated with the dystrophin-glycoprotein complex at astrocytic endfeet
    Ilja Boor
    Department of Pediatrics Child Neurology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
    Acta Neuropathol 114:403-10. 2007
    ..We demonstrated a direct protein interaction between MLC1 and Kir4.1. From these results we conclude that MLC1 is associated with the DGC at astrocytic endfeet...
  13. ncbi Vanishing white matter disease
    Marjo S van der Knaap
    Department of Pediatrics and Child Neurology, VU University Medical Center, Amsterdam, Netherlands
    Lancet Neurol 5:413-23. 2006
    ..Recently, undue activation of the unfolded-protein response has emerged as important in the pathophysiology of VWM, but the selective vulnerability of glia for defects in eIF2B is poorly understood...
  14. ncbi Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation: clinical and genetic characterization and target for therapy
    Laura van Berge
    1 Department of Child Neurology, VU University Medical Centre, Neuroscience Campus, Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
    Brain 137:1019-29. 2014
    ..A compound screen established a 'proof of principle' that the splice site mutation can be influenced. This finding is promising for future therapeutic strategies. ..
  15. doi Leukoencephalopathy with vanishing white matter: a review
    Marianna Bugiani
    Departments of Pediatrics, VU University Medical Center, Amsterdam, The Netherlands
    J Neuropathol Exp Neurol 69:987-96. 2010
    ..In view of the fact that VWM genes are housekeeping genes, it is surprising that the disease is primarily a leukoencephalopathy. The pathophysiology of selective glial vulnerability in VWM remains poorly understood...
  16. doi Megalencephalic leucoencephalopathy with cysts: defect in chloride currents and cell volume regulation
    Margreet C Ridder
    Department of Child Neurology, VU University Medical Center, 1081 HV Amsterdam, The Netherlands
    Brain 134:3342-54. 2011
    ....
  17. ncbi Defective glial maturation in vanishing white matter disease
    Marianna Bugiani
    Department of Pediatrics Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
    J Neuropathol Exp Neurol 70:69-82. 2011
    ..We also demonstrated a significant increase in numbers of premyelinating oligodendrocyte progenitors in VWM, which may explain the coexistence of oligodendrocytosis and myelin paucity in the patients' white matter...
  18. ncbi Megalencephalic leukoencephalopathy with cysts without MLC1 defect
    Marjo S van der Knaap
    Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
    Ann Neurol 67:834-7. 2010
    ..They lacked motor decline. Five had normal intelligence; 3 displayed cognitive deficiency. In conclusion, 2 phenotypes can be distinguished among the non-MLC1 mutated MLC patients: a classical and a benign phenotype...
  19. ncbi MLC1: a novel protein in distal astroglial processes
    P K Ilja Boor
    Department of Pediatrics Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
    J Neuropathol Exp Neurol 64:412-9. 2005
    ..Elucidation of the function of MLC1 will contribute to a better understanding of not only the pathophysiology of the disease, but also the role of astrocytes in normal neural tissue...
  20. ncbi Fright is a provoking factor in vanishing white matter disease
    Gerre Vermeulen
    Department of Pediatrics Child Neurology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands
    Ann Neurol 57:560-3. 2005
    ..These episodes typically are provoked by febrile infections or minor head trauma. We report on two patients who experienced an episode of rapid neurological deterioration after a fright...
  21. doi Vanishing white matter disease: the first reported chinese patient
    Sheila S N Wong
    Department of Paediatrics and Adolescent Medicine, United Christian Hospital, Kowloon, Hong Kong SAR, China
    J Child Neurol 23:710-4. 2008
    ..We describe the first Chinese patient with typical clinical and radiological features genetically confirmed to have vanishing white matter disease for a mutation in EIF2B4, followed by a brief review of the disease...
  22. ncbi Leukoencephalopathy with vanishing white matter due to homozygous EIF2B2 gene mutation. First Polish cases
    Hanna Mierzewska
    Division of Metabolic Disease, Department of Pediatrics, The Children s Memorial Health Institute, Aleja Dzieci Polskich 20, 04 730 Warsaw, Poland
    Folia Neuropathol 44:144-8. 2006
    ..A homozygous point mutation in the EIF2B2 gene was found, 638A>G. Both the parents were found to be carriers of this mutation. This is the first description of a Polish family with VWM...
  23. ncbi Translation matters: protein synthesis defects in inherited disease
    Gert C Scheper
    Department of Child Neurology Center for Neurogenomics and Cognitive Research, Vrije Universiteit Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands
    Nat Rev Genet 8:711-23. 2007
    ..Given the numerous proteins involved in mRNA translation, it is likely that further inherited diseases will turn out to be caused by mutations in genes that are involved in this complex process...
  24. ncbi Non-eIF2B-related cystic leukoencephalopathy of unknown origin
    Marjo S van der Knaap
    Ann Neurol 59:724. 2006
  25. pmc The N and C termini of the splice variants of the human mitogen-activated protein kinase-interacting kinase Mnk2 determine activity and localization
    Gert C Scheper
    Division of Molecular Physiology, Faculty of Life Sciences, University of Dundee, Dundee, United Kingdom
    Mol Cell Biol 23:5692-705. 2003
    ..Within the nucleus, Mnk2b and certain variants of Mnk2a that are present in the nucleus colocalize with the promyelocytic leukemia protein PML, which also binds to eIF4E...
  26. ncbi Localisation and regulation of the eIF4E-binding protein 4E-BP3
    Miranda Kleijn
    Division of Molecular Physiology, School of Life Sciences, University of Dundee, DD1 5EH, Dundee, UK
    FEBS Lett 532:319-23. 2002
    ..Furthermore, 4E-BP3/eIF4E association in the cytoplasm was regulated by serum or interleukin-2 starvation in the different cell types. Rapamycin did not affect the association of eIF4E with 4E-BP3 in the cytoplasm or in the nucleus...
  27. ncbi Does phosphorylation of the cap-binding protein eIF4E play a role in translation initiation?
    Gert C Scheper
    Division of Molecular Physiology, School of Life Sciences, University of Dundee, MSI WTB complex, Dow Street, UK
    Eur J Biochem 269:5350-9. 2002
    ..The implications of these studies are discussed in the light of other, in vitro and in vivo, investigations designed to address the role of eIF4E phosphorylation in mRNA translation or its control...