ArticleHuman mutation2020
Type II Alexander disease caused by splicing errors and aberrant overexpression of an uncharacterized GFAP isoform.
Article in Human mutation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- The Role of Glial Fibrillary Acidic Protein in the Neuropathology of Alzheimer's Disease and Its Potential as a Blood Biomarker for Early Diagnosis and Progression.Molecular neurobiology · 2025Review
- Genotype-Phenotype Association for 14Neurology. Genetics · 2025Article
- The GFAP proteoform puzzle: How to advance GFAP as a fluid biomarker in neurological diseases.Journal of neurochemistry · 2025Review
- Molecular Mechanisms in the Design of Novel Targeted Therapies for Neurodegenerative Diseases.Current issues in molecular biology · 2024Review
- GFAP as Astrocyte-Derived Extracellular Vesicle Cargo in Acute Ischemic Stroke Patients-A Pilot Study.International journal of molecular sciences · 2024Article
- Glial fibrillary acidic protein in Alzheimer's disease: a narrative review.Brain communications · 2024Review
- Stability dynamics of neurofilament and GFAP networks and protein fragments.Current opinion in cell biology · 2023Review
- Introns and Their Therapeutic Applications in Biomedical Researches.Iranian journal of biotechnology · 2023Review
- Identification of a novel de novo pathogenic variant in GFAP in an Iranian family with Alexander disease by whole-exome sequencing.European journal of medical research · 2022Review
- Effects of Alexander disease-associated mutations on the assembly and organization of GFAP intermediate filaments.Molecular biology of the cell · 2022Article
- Altered Spinal Homeostasis and Maladaptive Plasticity in GFAP Null Mice Following Peripheral Nerve Injury.Cells · 2022Article
- Alexander disease: models, mechanisms, and medicine.Current opinion in neurobiology · 2022Review
- Case report: Alexander's disease with "head drop" as the main symptom and literature review.Frontiers in neurology · 2022Article
- New GFAP splice isoform (GFAPµ) differentially expressed in glioma translates into 21 kDa N-terminal GFAP protein.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Review
- GFAP at 50.ASN neuroReview
Corrections and comments
- Erratum issued
Authors and funding
18 authors at 8 institutions in 3 countries.
Funding
Abstract
Alexander disease results from gain-of-function mutations in the gene encoding glial fibrillary acidic protein (GFAP). At least eight GFAP isoforms have been described, however, the predominant alpha isoform accounts for ∼90% of GFAP protein. We describe exonic variants identified in three unrelated families with Type II Alexander disease that alter the splicing of GFAP pre-messenger RNA (mRNA) and result in the upregulation of a previously uncharacterized GFAP lambda isoform (NM_001363846.1). Affected members of Family 1 and Family 2 shared the same missense variant, NM_001363846.1:c.1289G>A;p.(Arg430His) while in Family 3 we identified a synonymous variant in the adjacent nucleotide, NM_001363846.1:c.1290C>A;p.(Arg430Arg). Using RNA and protein analysis of brain autopsy samples, and a mini-gene splicing reporter assay, we demonstrate both variants result in the upregulation of the lambda isoform. Our approach demonstrates the importance of characterizing the effect of GFAP variants on mRNA splicing to inform future pathophysiologic and therapeutic study for Alexander disease.
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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.