Open Access

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

  • Published online on: June 8, 2021     https://doi.org/10.3892/mmr.2021.12211
  • Article Number: 572
  • Copyright: © Song et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


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.
View Figures
View References

Related Articles

Journal Cover

August-2021
Volume 24 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

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