OBJECTIVE: To explore the genetic basis of three children with unexplained developmental delay/intellectual disability (DD/ID). METHODS: Peripheral blood samples were collected from the patients and subjected to chromosomal microarray analysis (CMA). RESULTS: Patient 1 was found to harbor a 190 kb deletion at 9q34.3, which encompassed most of EHMT1 (OMIM 607001), the key gene for Kleefstra syndrome (OMIM 610253). Patients 2 and 3 were siblings. CMA showed that they have shared four chromosomal copy number variations (CNVs) including a deletion at 9q34.3 which spanned 154 kb and 149 kb, respectively, and encompassed the EHMT1 and CACNA1B (OMIM 601012) genes. The remaining 3 CNVs were predicted to be with no clinical significance. CONCLUSION Microdeletions at 9q33.4 probably underlay the pathogenesis of DD/ID in the three children, for which EHMT1 may be the key gene.
Child ; Chromosome Deletion ; Chromosomes, Human, Pair 9 ; Craniofacial Abnormalities/genetics* ; DNA Copy Number Variations ; Developmental Disabilities/genetics* ; Heart Defects, Congenital ; Humans ; Intellectual Disability/genetics*

Objective To investigate the differential expression of miR-124-3p in peripheral blood and clinical sig-nificance of patients with β-thalassemia.Methods Peripheral blood samples were collected from 33 patients with β-thalassemia and 30 healthy controls in Ningde Municipal Hospital Affiliated to Ningde Normal University from June 2021 to August 2022.The expression level of miR-124-3p was detected.Luciferase reporter gene was used to verify the interaction between miR-124-3p and ERF 3'UTR.The correlation between differential expression of miR-124-3p and β-thalassemia was analyzed and the clinical diagnostic value of miR-124-3p for β-thalassemia was eval-uated.Results Compared with healthy control individuals,the expression of miR-124-3p was significantly up-reg-ulated in patients with β-thalassemia(P＜0.001).The genotype of miR-124-3p high expression group was 84.2%β0(16/19),the genotype of low expression group was 55.6%β+(10/18).ROC curve analysis showed that miR-124-3p had predictive efficacy for β-thalassemia(AUC:0.842).Luciferase reporter gene analysis showed that ERF gene was the regulatory target of miR-124-3p.Conclusions The differential expression of miR-124-3p in patients with β-thalassemia is closely related to the genotype and clinical severity of thalassemia,and ERF is negatively reg-ulated by miR-124-3p.miR-124-3p may be an effective diagnostic biomarker for β-thalassemia.

[Objective] The aim of this study was to investigate the protective role of programmed cell death ligand-1 (PD-L1) in a mouse model of spinal cord injury (SCI) by regulating T cell immunity and the PI3K/Akt/mTOR signaling pathway. [Methods] C57BL/6 mice used to establish SCI models were divided into the sham operation group (Sham), SCI group, SCI+ PD-L1 antibody group (SCI+ Ab), and SCI+ PD-L1 protein group (SCI+ PRO). c57BL/6 mice and PD-L1 knockout mice were used for SCI mapping, and they were divided into the sham operation group (Sham WT), PD-L1 knockout sham operation group (Sham PD-L1 KO), SCI model group (SCI WT), and PD-L1 knockout SCI model group (SCI PD-L1 KO). Western blotting and qRT-PCR were applied to detect the expression of PD-L1 in spinal cord tissues at different time points after SCI; mouse motor function was assessed by the Basso Mouse Motor Scale (BMS); changes in the levels of inflammatory factors and T-cell subpopulations after SCI were analyzed using qRT-PCR and flow cytometry; and Western blotting was used to detect changes in the PI3K/Akt/mTOR signaling pathway activation. [Results] PD-L1 expression was upregulated in spinal cord tissues of mice subjected to SCI palliation, peaking on day 7. Compared with the SCI PD-L1 KO group, mice in the SCI WT group had significantly higher BMS scores at 7, 14, and 28 days after SCI (P<0.05), and the levels of inflammatory factors IL-1α, IL-2, IFN-γ and TNF-α were significantly lower on day 7 after palpation (P<0.05). Compared with the SCI+ PBS group, mice in the SCI+ PRO group had significantly higher Foxp3 levels and significantly lower Th1 and Th17 levels. Foxp3 levels were significantly higher, but Th1 and Th17 cell levels were significantly lower, and Th2 and Treg cell levels were significantly higher (P<0.05). The phosphorylation of the PI3K/Akt/mTOR signaling pathway was significantly higher in the SCI WT group mice than the SCI PD-L1 KO group ones (P<0.05). In contrast, the phosphorylation of PI3K/Akt/mTOR signaling pathway was significantly lower in the SCI+ PRO group than in the SCI+ PBS group and the SCI+ Ab group (P<0.05). [Conclusion] PD-L1 plays a neuroprotective role by regulating the balance of Th1, Th17, Th2 and Treg cells and inhibiting the PI3K/Akt/mTOR signaling pathway, thereby reducing the inflammatory response after SCI. PD-L1 is expected to be a new target for the treatment of SCI.