ArticleHuman genetics2005
Heightened stress response in primary fibroblasts expressing mutant eIF2B genes from CACH/VWM leukodystrophy patients.
Article in Human genetics, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 83 citations in OpenAlex.
- White matter disorders at the intersection of transcription, RNA processing and translation.Nature reviews. Neurology · 2026Review
- A scoping review of stem cell models of leukodystrophies: advances in understanding pathophysiological mechanisms.NPJ genomic medicine · 2025Article
- Regulation and function of elF2B in neurological and metabolic disorders.Bioscience reports · 2022Review
- Autophagy in white matter disorders of the CNS: mechanisms and therapeutic opportunities.The Journal of pathology · 2021Review
- Unfolded protein response in myelin disorders.Neural regeneration research · 2020Review
- Suppression of MEHMO Syndrome Mutation in eIF2 by Small Molecule ISRIB.Molecular cell · 2020Article
- Hyperinsulinaemic hypoglycaemia: A rare association of vanishing white matter disease.JIMD reports · 2020Article
- eIF2B Mutations Cause Mitochondrial Malfunction in Oligodendrocytes.Neuromolecular medicine · 2019Article
- Article
- Vanishing white matter: a leukodystrophy due to astrocytic dysfunction.Brain pathology (Zurich, Switzerland) · 2018Review
- Article
- Adult mouse eIF2Bε Arg191His astrocytes display a normal integrated stress response in vitro.Scientific reports · 2018Article
- Drug Screening Identifies Sigma-1-Receptor as a Target for the Therapy of VWM Leukodystrophy.Frontiers in molecular neuroscience · 2018Article
- Mitochondrial malfunction in vanishing white matter disease: a disease of the cytosolic translation machinery.Neural regeneration research · 2017Article
- Endoplasmic reticulum stress and eIF2α phosphorylation: The Achilles heel of pancreatic β cells.Molecular metabolism · 2017Review
- Leukodystrophies: a proposed classification system based on pathological changes and pathogenetic mechanisms.Acta neuropathologica · 2017Review
- EIF2S3 Mutations Associated with Severe X-Linked Intellectual Disability Syndrome MEHMO.Human mutation · 2017Article
- Astrocytes are central in the pathomechanisms of vanishing white matter.The Journal of clinical investigation · 2016Article
- Paradoxical Sensitivity to an Integrated Stress Response Blocking Mutation in Vanishing White Matter Cells.PloS one · 2016Article
- Endoplasmic Reticulum Protein Quality Control Failure in Myelin Disorders.Frontiers in molecular neuroscience · 2016Review
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
Childhood ataxia with central nervous system hypomyelination (CACH), also called vanishing white matter (VWM) leukoencephalopathy, is a fatal genetic disease caused by mutations in eukaryotic initiation factor 2B (eIF2B) genes. The five subunits eIF2B factor is critical for translation initiation under normal conditions and regulates protein synthesis in response to cellular stresses. Primary fibroblasts from CACH/VWM patients and normal individuals were used to measure basal eIF2B activity as well as global protein synthesis and ATF4 induction in response to stress in the endoplasmic reticulum. We show that although the cells expressing mutant eIF2B genes respond normally to stress conditions by reduced global translation rates, they exhibit significantly greater increase in ATF4 induction compared to normal controls despite equal levels of stress and activity of the upstream eIF2alpha kinase. This heightened stress response observed in primary fibroblasts that suffer from minor loss of basal eIF2B activity may be employed as an initial screening tool for CACH/VWM leukodystrophy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.