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A report of two cases of bulbospinal form Alexander disease and preliminary exploration of the disease

  • Authors:
    • Xiaoxuan Song
    • Jingwen Jiang
    • Wotu Tian
    • Feixia Zhan
    • Zeyu Zhu
    • Binyin Li
    • Huidong Tang
    • Li Cao
  • View Affiliations / Copyright

    Affiliations: Department of Neurology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China
    Copyright: © Song et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 572
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    Published online on: June 8, 2021
       https://doi.org/10.3892/mmr.2021.12211
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Abstract

Alexander disease (AxD) is a cerebral white matter disease affecting a wide range of ages, from infants to adults. In the present study, two cases of bulbospinal form AxD were reported, and a preliminary exploration of AxD was conducted thorough clinical, functional magnetic resonance imaging (fMRI) and functional analyses. In total, two de novo mutations in the glial fibrillary acidic protein (GFAP) gene (c.214G>A and c.1235C>T) were identified in unrelated patients (one in each patient). Both patients showed increased regional neural activity and functional connectivity in the cerebellum and posterior parietal cortex according to fMRI analysis. Notably, grey matter atrophy was discovered in the patient with c.214G>A variant. Functional experiments revealed aberrant accumulation of mutant GFAP and decreased solubility of c.1235C>T variant. Under pathological conditions, autophagic flux was activated for GFAP aggregate degradation. Moreover, transcriptional data of AxD and healthy human brain samples were obtained from the Gene Expression Omnibus database. Gene set enrichment analysis revealed an upregulation of immune‑related responses and downregulation of ion transport, synaptic transmission and neurotransmitter homeostasis. Enrichment analysis of cell‑specific differentially expressed genes also indicated a marked inflammatory environment in AxD. Overall, the clinical features of the two patients with bulbospinal form AxD were thoroughly described. To the best of our knowledge, the brain atrophy pattern and spontaneous brain functional network activity of patients with AxD were explored for the first time. Cytological experiments provided evidence of the pathogenicity of the identified variants. Furthermore, bioinformatics analysis found that inflammatory immune‑related reactions may play a critical role in AxD, which may be conducive to the understanding of this disease.
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Copy and paste a formatted citation
Spandidos Publications style
Song X, Jiang J, Tian W, Zhan F, Zhu Z, Li B, Tang H and Cao L: A report of two cases of bulbospinal form Alexander disease and preliminary exploration of the disease. Mol Med Rep 24: 572, 2021.
APA
Song, X., Jiang, J., Tian, W., Zhan, F., Zhu, Z., Li, B. ... Cao, L. (2021). A report of two cases of bulbospinal form Alexander disease and preliminary exploration of the disease. Molecular Medicine Reports, 24, 572. https://doi.org/10.3892/mmr.2021.12211
MLA
Song, X., Jiang, J., Tian, W., Zhan, F., Zhu, Z., Li, B., Tang, H., Cao, L."A report of two cases of bulbospinal form Alexander disease and preliminary exploration of the disease". Molecular Medicine Reports 24.2 (2021): 572.
Chicago
Song, X., Jiang, J., Tian, W., Zhan, F., Zhu, Z., Li, B., Tang, H., Cao, L."A report of two cases of bulbospinal form Alexander disease and preliminary exploration of the disease". Molecular Medicine Reports 24, no. 2 (2021): 572. https://doi.org/10.3892/mmr.2021.12211
Copy and paste a formatted citation
x
Spandidos Publications style
Song X, Jiang J, Tian W, Zhan F, Zhu Z, Li B, Tang H and Cao L: A report of two cases of bulbospinal form Alexander disease and preliminary exploration of the disease. Mol Med Rep 24: 572, 2021.
APA
Song, X., Jiang, J., Tian, W., Zhan, F., Zhu, Z., Li, B. ... Cao, L. (2021). A report of two cases of bulbospinal form Alexander disease and preliminary exploration of the disease. Molecular Medicine Reports, 24, 572. https://doi.org/10.3892/mmr.2021.12211
MLA
Song, X., Jiang, J., Tian, W., Zhan, F., Zhu, Z., Li, B., Tang, H., Cao, L."A report of two cases of bulbospinal form Alexander disease and preliminary exploration of the disease". Molecular Medicine Reports 24.2 (2021): 572.
Chicago
Song, X., Jiang, J., Tian, W., Zhan, F., Zhu, Z., Li, B., Tang, H., Cao, L."A report of two cases of bulbospinal form Alexander disease and preliminary exploration of the disease". Molecular Medicine Reports 24, no. 2 (2021): 572. https://doi.org/10.3892/mmr.2021.12211
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