Clinical report and genetic analysis of a Chinese patient with developmental and epileptic encephalopathy associated with novel biallelic variants in the ST3GAL3 gene.

BACKGROUND: Defects in the Golgi enzyme beta-galactoside-alpha-2,3-sialyltransferase-III (ST3Gal-III) caused by biallelic ST3GAL3 gene variants are associated with human neurodevelopmental disorders. Although ST3GAL3 gene variants have been linked to developmental and/or epileptic encephalopathy 15 (DEE15), their presence has only been reported in nine patients; however, the real frequency may be masked by insufficient screening. METHODS: Phenotypic information was collected from a male patient with severe psychomotor developmental delay and epileptic seizures, and genetic testing was done using whole exome sequencing. A molecular dynamics simulation analysis was performed to assess the potential impacts of the identified ST3GAL3 variants on the ST3Gal-III protein function, and a literature review was conducted to compare this case with previously described cases and assess disease manifestation and genetic characteristics. RESULTS: The patient inherited compound heterozygous ST3GAL3 gene variants, NM_006279.5:c.809G>A (p.Arg270Gln) and c.921dupG (p.Thr308fs*8). Neither variant had been previously reported in the general population. The p.Arg270Gln variant disrupted a hydrogen bond in the simulated ST3Gal-III protein structure. Among 25 patients with ST3GAL3 gene defects, eight ST3GAL3 gene variants were identified, and five variants had DEE signs. CONCLUSION: Patients with DEE15 may have novel ST3GAL3 gene variants, and this study may be the first clinical report of their occurrence in a Chinese patient. These variants should be considered when evaluating patients presenting with unexplained early-onset epileptic encephalopathy, severe developmental delay, and/or intellectual disability.

[Clinical report and genetic analysis of a child with Aicardi-Goutières syndrome type 3 due to compound heterozygous variants of RNASEH2C gene].

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a child with Aicardi-Goutières syndrome 3 (AGS3). METHODS: Trio whole exome sequencing was carried out for the child and his parents, and candidate variants were verified by Sanger sequencing. To further clarify their pathogenicity, the crystal structure of the variants was simulated and analyzed, and the plasmid of variants was expressed in vitro. A literature search was also carried out to summarize the phenotypic and genetic characteristics of AGS3. RESULTS: The child was found to harbor novel compound heterozygous variants of the RNASEH2C gene, namely c.434G>T (p.Arg145Leu) and c.494G>C (p.Ter165Ser), which were inherited from his mother and father, respectively. Analysis of protein crystal structure suggested that the c.434G>T (p.Arg145Leu) variant may affect the stability of local structure, and in vitro experiments showed that this variant can lead to protein degradation. The c.494G>C (p.Ter165Ser) variant has destroyed the stop codon, resulting in prolonged variant. CONCLUSION: The novel compound heterozygous variants of the RNASEH2C gene probably underlay the AGS3 in this child, which has enriched the phenotypic and mutational spectrum of this disorder.

Effects of microRNA-101-3p on predicting pediatric acute respiratory distress syndrome and its role in human alveolar epithelial cell.

Pediatric acute respiratory distress syndrome (PARDS) is a severe form of respiratory failure associated with high mortality among children. The objective of this study is reported to explore the clinical function and molecular roles of microRNA-101-3p (miR-101-3p) in PARDS. The levels of miR-101-3p and mRNA levels of SRY-related high-mobility group box 9 (Sox9) were measured by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Additionally, the diagnostic role of miR-101-3p was identified by using the Receiver operating characteristic (ROC) curve. The cell proliferation and apoptosis were examined through Cell Counting Kit-8 (CCK-8) assay and flow cytometry. To detect inflammation in cells, enzyme-linked immunosorbent assays (ELISA) were performed. The target gene of miR-101-3p was confirmed through data obtained from the luciferase activity. In patients with PARDS, miR-101-3p expression was decreased. Moderate and severe PARDS patients had lower levels of miR-101-3p than mild PARDS patients. The inflammatory progression was related to the aberrant expression of miR-101-3p in all PARDS children. MiR-101-3p was highly predictive for the detection of children with PARDS. In addition, miR-101-3p might protect A549 cells from abnormal proliferation, apoptosis, and inflammation caused by lipopolysaccharide (LPS). Sox9 might be a target gene of miR-101-3p and increased mRNA expression of Sox9 in LPS-treated A549 cells was inhibited by overexpression of miR-101-3p. Ultimately, this study suggested that reduced expression of miR-101-3p plays a role in PARDS, providing a novel angle to study the disease.

The effects of the atomization inhalation of budesonide, salbutamol, and ipratropium bromide on the T-lymphocyte subset and inflammatory cytokine levels in children with asthmatic pneumonia.

OBJECTIVE: This study aimed to explore the effects of the atomization inhalation of budesonide (BUD), salbutamol (SAL), and ipratropium bromide (IB) on the T-lymphocyte subset and inflammatory cytokine levels in children with asthmatic pneumonia (AP). METHODS: A total of 118 children with AP admitted to our hospital were selected as the study cohort and randomly divided into two groups. The study group, included 67 patients who were treated with the atomization inhalation of BUD, SAL, and IB. The control group, included 51 patients who were treated with the atomization inhalation of BUD. The two groups were compared in terms of their symptom disappearance times, the therapeutic effects, inflammatory cytokine changes, their pulmonary function indices [C-reactive protein (CRP), respiratory frequency, forced vital capacity (FVC), one-second forced expiratory volume (FEV1), blood oxygen saturation (SpO2)], and their T-lymphocyte subset levels before and after the treatment, and the incidences of adverse reactions after the treatment. RESULTS: The symptom disappearance times in the study group were shorter than they were in the control group (P<0.05), and the overall response rate (ORR) was significantly higher in the study group (P<0.05). The IL-5, IL-6, and IL-10 levels were all lower in the study group (P<0.05), but the interferon-γ levels were higher in this group (P<0.05). The CRP level was lower in the study group (P<0.05), but the FVC, FEV1, and SpO2 levels were higher in this group (P<0.05). After the treatment, the CD3+, CD4+ and CD4+/CD8+ levels were all higher in the study group (P<0.05), but the CD8+ level was lower in this group (P<0.05). The incidence of adverse reactions in the study group was lower than it was in the control group (P=0.014). CONCLUSION: The atomization inhalation of BUD, SAL, and IB is markedly effective in treating children with AP, and it can improve their immune function and reduce their inflammatory cytokines levels.

[Application of surface electromyography in children with dysphagia].

OBJECTIVE: To study the application value of surface electromyography in children with dysphagia. METHODS: A total of 20 children with dysphagia were enrolled as the observation group, and 20 healthy children, matched for sex and age, were enrolled as the control group. Surface electromyography was used to record the electromyography integral values of the submental and infrahyoid muscle groups in the resting state and the state after water swallowing. The two groups were compared in terms of the electromyography integral values of the submental and infrahyoid muscle groups in the resting state and the state after swallowing 5 mL water. The observation group was observed in terms of the changes in the electromyography integral values of the submental and infrahyoid muscle groups after 1 month of rehabilitation treatment. A Spearman correlation analysis was used to evaluate the correlation of the degree of dysphagia with the electromyography integral values of the submental and infrahyoid muscle groups in the observation group. RESULTS: There was no significant difference between the two groups in the electromyography integral values of the submental and infrahyoid muscle groups in the resting state (P>0.05), while after water swallowing, the observation group had significantly higher electromyography integral values than the control group (P<0.05). The observation group had significant improvements in the clinical symptoms of dysphagia after treatment, with significant reductions in the electromyography integral values of the submental and infrahyoid muscle groups (P<0.05). The severity of dysphagia was positively correlated with the electromyography integral values of the submental and infrahyoid muscle groups (P<0.01). CONCLUSIONS: Surface electromyography is useful in the diagnosis and therapeutic effect evaluation for dysphagia in children.