Background: Spinal neurofibromatosis (SNF) is a related form of Neurofibromatosis type 1 (NF1) with a low incidence. Here, we report a SNF patient with NF1 (OMIM *613113) mutation in a classic NF1 family to enrich the case data. Methods: We presented the clinical data of a 27-year-old female suffered from SNF.Two NF1 individuals (the mother and the brother) in the patient's family were also described. In the SNF patient, tumors in cervical were removed by surgical operation after the spinal MRI evaluation. Hematoxylin-eosin staining and immunohistochemistry were performed to better characterize the excised tumors. NF1 exons of the patient and her NF1 families were further sequenced by the next-generation sequencing technology. Results: The patient developed irregular café-au-lait macules, multi-subcutaneous nodules, recurrent numbness, and weakness of both lower extremities. Multiple neurofibromas were found in the whole spine by spinal MRI. Tumor-like cells and hyperplasia of ganglion cells were found in the excised tissue by H&E staining and immunohistochemistry, respectively. One-year follow-up on the SNF patient showed that after the surgery lower limb pain, numbness and convulsion were completely relieved. A common germ-line pathogenic mutation (NM_000267.3:c.1721 + 3A>G) was found in both the SNF patient and her classic NF1 families. Conclusion: A case of SNF with classic NF1 mutation in a classic NF1 family was identified for the first time, indicating that SNF may share the same gene mutation with NF1, while the different manifestation of NF1 and SNF may be related to gene modification. K E Y W O R D Sclassic neurofibromatosis type 1, NF1 gene mutation, spinal neurofibromatosis 2 of 7 | NING et al.

Background Evaluate the effect of the miRNA-106a/20b on the efficacy of DCs pulsed with GSCs in activating GSC-specific T cell responses. Methods We cultured GSCs and prepared GSC antigen lysates by apoptosis. Then, immature DCs were pulsed with GSC antigen lysates in vitro. STAT3 levels in DCs were assessed by Western blotting, and the expression of CD80, CD86, and MHC-II was tested by fluorescence-activated cell sorting. The production and secretion of the cytokines IL-6, IL-12, TNF- α , and IL-10 in DCs induced by GSCs were determined by enzyme-linked immunosorbent assay. Finally, the cytotoxic functions of T cells stimulated by GSC-DC fusion cells transfected with a miR-106a/20b mimic in vitro and the antitumour activity in vivo were detected. Results We found that the levels of miR-106a/20b were downregulated, but the expression of STAT3 was significantly upregulated. Simultaneously, the inhibition of STAT3 in the fusion cells by STAT3-specific siRNA caused significant upregulation of the expression of CD80, CD86, and MHC-II, and the secretion of the cytokines IL-6 and IL-12 was substantially increased, IL-10 was markedly decreased. These findings revealed that STAT3 is an important regulator of DC maturation. Furthermore, the interactional binding sites between the 3′-untranslated region (3′-UTR) of STAT3 mRNA and miR-106a/20b were predicted by bioinformatics and verified by a dual-luciferase assay. Moreover, the reduction in STAT3 levels in GSC-DCs enhanced the generation of CD8+ T cells and reduced the generation of Foxp3+ regulatory T cells. Meanwhile, the secretion of the T cell cytokine IFN- γ was significantly increased. Further research showed that DCs after miR-106a/20b-mimics transfection could promote the inhibition of GSC proliferation by T cells in vitro and suppress tumour growth in vivo. Conclusions This study indicted that the miR-106a/20b activation could be one of the important molecular mechanisms leading to enhance antitumour immune responses of GSC-mediated DCs, which downregulated the expression of STAT3 to alleviate its the inhibitory effect.

No abstract