An insertion mutation of the MECP2 gene in severe neonatal encephalopathy and ocular and oropharyngeal dyskinesia: a case report.

BACKGROUND: Pathogenic variation of the MECP2 gene presents mostly as Rett syndrome in females and is extremely rare in males. Most male patients with MECP2 gene mutation show MECP2 duplication syndrome. CASE PRESENTATION: Here we report a rare case in a 10-month-old boy with a hemizygous insertion mutation in MECP2 as NM_001110792, c.799_c.800insAGGAAGC, which results in a frameshift mutation (p.R267fs*6). The patient presented with severe encephalopathy in the neonatal period, accompanied by severe development backwardness, hypotonia, and ocular and oropharyngeal dyskinesia. This is the first report of this mutation, which highlights the phenotype variability associated with MECP2 variants. CONCLUSIONS: This case helps to expand the clinical spectrum associated with MECP2 variants. Close attention should be paid to the growth and development of patients carrying a MECP2 variant or Xq28 duplication. Early interventions may help improve symptoms to some certain extent.

Association of Cytomegalovirus Infection with Lenticulostriate Stroke After Mild Head Trauma in Young Children.

The development of lenticulostriate stroke following mild head trauma accounts for 3% of traumatic brain injuries in children. Nevertheless, the pathogenesis of infantile lenticulostriate stroke with lenticulostriate calcification is poorly understood. In this study, we explored the association of a recent viral infection with the development of infantile lenticulostriate stroke with lenticulostriate calcification following mild head trauma in children. We examined the records for 49 children (<36 months old) diagnosed with infantile stroke following mild head trauma at the First Hospital of Jilin University between January 2007 and August 2019. The demographic characteristics, clinical manifestations, and laboratory and imaging results were collected and analyzed. Antibodies against Epstein-Barr virus, herpes simplex virus, and cytomegalovirus in the patient sera were assessed. A total of 18 patients with lenticulostriate stroke and calcification were included in the Patient group (16.61 ± 10.57 months), and 14 patients without calcification were included in the Control group (13.07 ± 7.66 months). Imaging findings demonstrated the presence of lenticulostriate stroke in all patients. There were no significant differences in the demographic characteristics or clinical manifestations of stroke between both groups (P > .05). Similarly, no significant differences were observed in the Epstein-Barr virus and herpes simplex virus-1 antibody positivity in both groups. In contrast, cytomegalovirus antibody was significantly more abundant in the Patient group (P < .05). All patients were hospitalized for conservative treatment with favorable prognoses. Our results suggest that cytomegalovirus infection may be associated with the development of lenticulostriate strokes in pediatric patients following minor head injury.

Late-onset Leigh syndrome without delayed development in China: A case report.

BACKGROUND: Leigh syndrome (LS) is one of the most common mitochondrial diseases in infants and children. LS often manifests as early-onset with delayed phenotypic development. However, late-onset LS with normal development and white matter lesions in the brain is rarely reported, thereby highlighting the phenotypic variability of LS expression. CASE SUMMARY: We report a 12-year-old boy who presented with an unusual late-onset and fulminant form of LS that is maternally inherited without developmental delay. The patient was admitted to the hospital with symptoms of ptosis and somnolence, and died within 2 mo. Analysis of peripheral blood leukocytes showed a homoplasmic m.9176T>C mutation in the patient. Magnetic resonance imaging also revealed lesions in bilateral white matter as well as symmetrical lesions in the basal ganglia and brain stem. The patient was diagnosed with LS. The patient was treated with vitamin C, vitamin D, and adenosine-triphosphate. The patient died within 2 mo of hospital admission. CONCLUSION: LS can present in both infants and older children with different phenotypes.

Case Report: m.13513 G>A Mutation in a Chinese Patient With Both Leigh Syndrome and Wolff-Parkinson-White Syndrome.

A number of causative mutations in mitochondrial and nuclear DNA have been identified for Leigh syndrome, a neurodegenerative encephalopathy, including m. 8993 T>G, m.8993 T>C, and m.3243A>G mutations in the MTATP6, MTATP6, and MT-TL1 genes, respectively, which have been reported in Leigh syndrome patients in China. The m.13513 G>A mutation has been described only a few times in the literature and not previously reported in China. Here we report the case of a 15-month-old boy who presented with ptosis and developmental delay and was diagnosed with Leigh syndrome and well as Wolff-Parkinson-White (WPW) syndrome. The m.13513 G>A mutation was found in DNA from blood. He was intubated due to respiratory failure and died at 23 months of age. The m.13513 G>A mutation in the ND5 gene of mitochondrial DNA is associated with Leigh syndrome and WPW syndrome; however, this is the first report of this mutation in a patient in China, highlighting the geographical and racial variability of Leigh syndrome.

Inflammatory response in epilepsy is mediated by glial cell gap junction pathway (Review).

Epilepsy is a common neurological disease that affects more than 50 million people worldwide. Neuro-inflammation plays an important role in epilepsy. Activation of the immune system and an excessive inflammatory response can increase the frequency of seizures and increase the susceptibility to epilepsy. Therefore, anti-inflammatory therapies may have antiepileptic effects. Connexin 43 (Cx43) is a major component of astroglial hemichannels and gap junctions. Gap junctions are important for the direct exchange of substances and information between cells, as well as regulating the neuroinflammatory response, changing neuronal excitability, neuronal apoptosis, and synaptic remodeling. Cx43-mediated gap junction pathway can be crucial in epilepsy-induced neuroinflammatory cascades. Further, pro-inflammatory cytokines may in turn directly affect the expression of the Cx43 protein in astrocytes. Therefore, examining the association between neuroinflammation and epilepsy can be instrumental in uncovering the pathogenesis of epilepsy, which can lead to the development of novel and more effective antiepileptic drugs.

Synergistic effects of Rho kinase inhibitor Y-27632 and Noggin overexpression on the proliferation and neuron-like cell differentiation of stem cells derived from human exfoliated deciduous teeth.

Stem cells from human exfoliated deciduous teeth (SHEDs) are highly proliferative, clonogenic, and multipotent stem cells with a neural crest cell origin. This property could be a desirable option for potential therapeutic applications. In this study, we focus on the effects of Rho kinase inhibitors Y-27632 and Noggin on the proliferation of SHEDs and their differentiation into neuron-like cells. SHEDs were extracted from 10 samples of deciduous teeth obtained from healthy children aged from 5 to 10. The passaged SHEDs were transfected with Noggin, Y-27632, or their combination. By means of MTT and colony formation assays, the effects of Y-27632 and Noggin on cell viability and colony formation were detected. Cellular morphology and neurosphere formation were observed under a microscope. Y-27632 transfection in SHEDs showed enhanced cell viability, colony formation, and neurosphere formation indicating that Y-27632 could promote cell proliferation of SHEDs. Furthermore, we observed that the SHEDs treated with Noggin in combination with Y-27632 displayed typical neuron-like cell morphology and reticular processes. Noggin or Y-27632 alone or in combination induced obviously increased NSE, Nestin, and GFAP levels, which were highest in SHEDs treated with the combination of Noggin and Y-27632. These findings suggest that Y-27632 promotes the proliferation of SHEDs, and Y-27632 and Noggin in combination have a synergistic effect on promoting differentiation of SHEDs into neuron-like cells.

Extracellular Vesicle-Derived microRNA-410 From Mesenchymal Stem Cells Protects Against Neonatal Hypoxia-Ischemia Brain Damage Through an HDAC1-Dependent EGR2/Bcl2 Axis.

Hypoxia-ischemia brain damage (HIBD) is a neurological disorder occring in neonates, which is exacerbated by neuronal apoptosis. Mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) have been proposed as a promising strategy for treating or preventing ischemia-related diseases. However, their mechanisms in HIBD remain unclear. Thus, we aimed to address the role of EV-derived microRNA (miR)-410 in HIBD. Neonatal HIBD mouse model was constructed using HI insult, from which neurons were isolated, followed by exposure to oxygen glucose deprivation (OGD). EVs were isolated from human umbilical cord (hUC)-derived MSCs. In silico analyses, dual-luciferase reporter gene and chromatin immunoprecipitation assays were adopted to determine relationships among miR-410, histone deacetylase 1 (HDAC1), early growth response protein 2 (EGR2), and B cell lymphoma/leukemia 2 (Bcl2). The functional roles of EV-derived miR-410 were determined using loss- and gain-of functions experiments, and by evaluating neuronal viability, cell-cycle distribution and neuronal apoptosis in vitro as well as modified neurological severity score (mNSS), edema formation, and cerebral infarction volume in vivo. hUC-MSCs-derived EVs protected against HIBD in vivo and inhibited the OGD-induced neuronal apoptosis in vitro. miR-410 was successfully delivered to neurons by hUC-MSCs-EVs and negatively targeted HDAC1, which inversely mediated the expression of EGR2/Bcl2. Upregulation of EV-derived miR-410 promoted the viability but inhibited apoptosis of neurons, which was reversed by HDAC1 overexpression. EV-derived miR-410 elevation reduced mNSS, edema formation, and cerebral infarction volume by increasing EGR2/Bcl2 expression through downregulating HDAC1 expression in vivo. In summary, EV-derived miR-410 impeded neuronal apoptosis by elevating the expression of EGR2/Bcl2 via HDAC1 downregulation, thereby providing a potential strategy for treating or preventing HIBD.