Case report: Two cases of Poirier-Bienvenu neurodevelopmental syndrome and review of literature.

The Poirier-Bienvenu neurodevelopmental syndrome (POBINDS) is a rare disease caused by mutations in the CSNK2B gene, which is characterized by intellectual disability and early-onset epilepsy. Mosaicism has not been previously reported in CSNK2B gene. POBINDS is autosomal dominant and almost all reported cases were de novo variants. Here, we report two patients were diagnosed with POBINDS. Using Whole Exome Sequencing (WES), we detected two novel CSNK2B variants in the two unrelated individuals: c.634_635del (p.Lys212AspfsTer33) and c.142C > T (p.Gln48Ter) respectively. Both of them showed mild developmental delay with early-onset and clustered seizures. The patient with c.634_635del(p.Lys212AspfsTer33) variant was mutant mosaicism, and the proportion of alleles in peripheral blood DNA was 28%. Further, the literature of patients with a de novo mutation of the CSNK2B gene was reviewed, particularly seizure semiology and genotype-phenotype correlations.

Phenotype-Genotype Analysis Based on Molecular Classification in 135 Children With Mitochondrial Disease.

OBJECTIVES: Over the past decades, mitochondrial disease classification has been mainly based on molecular defects. We aim to analyze phenotype-genotype correlation of mitochondrial disorders according to molecular classification. METHODS: In this cohort study, we identified 135 individuals diagnosed with mitochondrial disorders, and all patients were divided into four subgroups based on molecular functions: the Respiratory Chain group (including subunits and assembly proteins in the respiratory chain), the Protein Synthesis group (including mitochondrial RNA metabolism, mitochondrial translation), the mitcohindrial DNA (mtDNA) Replication group, and the Others group (including cofactors, homeostasis, substrates, and inhibitors). RESULTS: We found that in China, patients with the mtDNA variant constituted a large percentage of mitochondrial disease and were associated with a male preponderance in the Respiratory Chain group, whereas those in the Protein Synthesis group showed a relatively later onset and higher serum lactate level. In contrast, patients with nuclear DNA variants were younger at onset, with no specific lactate or cranial imaging features, especially in the Others group, which contained several mitochondrial diseases with corresponding treatment. CONCLUSION: The mtDNA was recommended to detect first in patients with typical lactate and cranial imaging features. A broader consideration and detection are necessary for a better prognosis in an atypical patient.

A pediatric case of primary amoebic meningoencephalitis due to Naegleria fowleri diagnosed by next-generation sequencing of cerebrospinal fluid and blood samples.

BACKGROUND: Primary amoebic meningoencephalitis (PAM) is a rare, acute and fatal disease of the central nervous system caused by infection with Naegleria fowleri (Heggie, in Travel Med Infect Dis 8:201-6, 2010). Presently, the majority of reported cases in the literature have been diagnosed through pathogen detection pathogens in the cerebrospinal fluid (CSF). This report highlights the first case of pediatric PAM diagnosed with amoeba infiltration within CSF and bloodstream of an 8-year-old male child, validated through meta-genomic next-generation sequencing (mNGS). CASE PRESENTATION: An 8-year-old male child was admitted to hospital following 24 h of fever, headache and vomiting and rapidly entered into a coma. CSF examination was consistent with typical bacterial meningitis. However, since targeted treatment for this condition proved to be futile, the patient rapidly progressed to brain death. Finally, the patient was referred to our hospital where he was confirmed with brain death. CSF and blood samples were consequently analyzed through mNGS. N. fowleri was detected in both samples, although the sequence copy number in the blood was lower than for CSF. The pathogen diagnosis was further verified by PCR and Sanger sequencing. CONCLUSIONS: This is the first reported case of pediatric PAM found in mainland China. The results indicate that N. fowleri may spread outside the central nervous system through a damaged blood-brain barrier.

Identification and Validation of a Dysregulated miRNA-Associated mRNA Network in Temporal Lobe Epilepsy.

OBJECTIVES: This study is aimed at exploring the relationships between miRNAs and mRNAs and to characterize their biological functions in temporal lobe epilepsy (TLE). METHODS: Novel clinical significant miRNAs and target genes and their potential underlying mechanisms have been discovered and explored by mining miRNAs and mRNA expression data of TLE patients using various bioinformatics methods. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to validate the bioinformatic analysis results. RESULTS: A total of 6 dysregulated miRNAs and 442 differentially expressed genes (DEGs) related to TLE were obtained from GEO database (GSE114701 and GSE127871 datasets). A protein-protein interaction (PPI) network containing the 442 DEGs was established. mRNA response elements from the 6 dysregulated miRNAs were predicted using the miRDB and TargetScan bioinformatic tools. By merging the identified targets of the dysregulated miRNAs and the 247 downregulated DEGs, a miRNA-mRNA network was constructed revealing the interaction of miR-484 with eight mRNAs (ABLIM2, CEP170B, CTD-3193O13.9, EFNA5, GAP43, PRKCB, FXYD7, and NCAN). A weighted correlation network analysis (WGCNA) based on the eight genes was established and demonstrated that these mRNAs, except FXYD7 and NCAN, were hub genes in the network. Gene Oncology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that the six hub genes were mainly involved in cellular-related biological functions and the neurotransmitter synapse pathway. The differences in expression levels of the miR-484 and the three hub genes (CTD-3193O13.9, EFNA5, and PRKCB) observed experimentally in TLE patients compared to those of healthy controls were consistent with the WGCNA prediction. CONCLUSION: Our study suggests that understanding the miRNA-mRNA interactions will provide insights into the epilepsy pathogenesis. In addition, our results indicate that miR-484 may be a promising novel biomarker for TLE.

[Research advances in hereditary epilepsy and precision drug therapy].

Epilepsy is a common nervous system disease. It has been found that the pathogenesis of epilepsy is associated mutations in various genes, including genes encoding voltage-dependent ion channel, genes encoding ligand-gated ion channel, and solute carrier family genes. Different types of epilepsy caused by different mutations have different responses to drugs, and therefore, diagnosis and medication guidance based on genes are new thoughts for developing therapies. With the application of next-generation sequencing technology, more and more genes will be determined, which helps to further study the pathogenic mechanism of mutant genes and provides a basis for precision drug therapy for epilepsy.

[Relationship between the expression of murine double minute 2 oncogene and non-Hodgkin lymphoma in childhood].

OBJECTIVE: To investigate the relationship between the expression of murine double minute 2 (MDM2) oncogene and non-Hodgkin lymphoma (NHL) in childhood. METHODS: Thirty-one cases of NHL were enrolled in this study as patient group and 8 cases of lymphadenitis as control group. (1) Immunohistochemistry ultrasensitive S-P assay was used to detect the expression of MDM2 protein in pathological tissues in all cases. Positive cells were dyed yellow or brown in nuclei. MDM2 positive cell was defined as >/= 10% of the tumor cells were positive, which was overexpression of MDM2 protein. (2) RT-PCR (reverse transcription-polymerase chain reaction) was performed to value the overexpression of MDM2 mRNA in the pathological tissues and mononuclear cells in peripheral blood. While the ratio of MDM2/beta-actin was >16% was defined as overexpression of MDM2 mRNA. RESULTS: (1) Rates of overexpression of MDM2 protein and MDM2 mRNA were 64.5% and 61.3%, respectively, which were significantly different as compared to that of control group (P < 0.05 and P < 0.01, respectively). (2) The relationship analysis among subgroups in the experiment group showed that the overexpression of MDM2 protein did not correlate with classifications of working formulation, cellular origin, sex, clinical stage and involved extranodal sites (P > 0.05), but significantly correlated with classifications of B status and the increased serum LDH level (P < 0.05). It was shown that the overexpression of MDM2 mRNA did not correlate with classifications of working formulation, cellular origin, sex and clinical stage (P > 0.05), significantly correlated with B status (P < 0.05), and was remarkably significantly correlated with the involved extranodal sites and the increased serum LDH level (P < 0.01). (3) It was demonstrated that the overexpression of MDM2 mRNA in the pathological tissues was similar to the overexpression of MDM2 protein in the pathological tissues and MDM2 mRNA in peripheral blood (P > 0.05, kappa = 0.655 and 0.571), and the overexpression of MDM2 protein in the pathological tissues was similar to that of MDM2 mRNA in peripheral blood (P > 0.05, kappa = 0.609). CONCLUSIONS: (1) The rate of MDM2 oncogene overexpression was quite high. (2) The overexpression of MDM2 protein in pathological tissues determined by using immunohistochemistry ultrasensitive S-P assay was similar to that of MDM2 mRNA in pathological tissues detected by using RT-PCR method. Both methods might be used to detect the overexpression of MDM2 oncogene in the cases of childhood NHL. (3) The overexpression of MDM2 oncogene related to the poor status and poor prognosis of patients with childhood NHL.