CHD4 variants are associated with childhood idiopathic epilepsy with sinus arrhythmia.

AIMS: CHD4 gene, encoding chromodomain helicase DNA-binding protein 4, is a vital gene for fetal development. In this study, we aimed to explore the association between CHD4 variants and idiopathic epilepsy. METHODS: Trios-based whole-exome sequencing was performed in a cohort of 482 patients with childhood idiopathic epilepsy. The Clinical Validity Framework of ClinGen and an evaluating method from five clinical-genetic aspects were used to determine the association between CHD4 variants and epilepsy. RESULTS: Four novel heterozygous missense mutations in CHD4, including two de novo mutations (c.1597A>G/p.K533E and c.4936G>A/p.E1646K) and two inherited mutations with co-segregation (c.856C>G/p.P286A and c.4977C>G/p.D1659E), were identified in four unrelated families with eight individuals affected. Seven affected individuals had sinus arrhythmia. From the molecular sub-regional point of view, the missense mutations located in the central regions from SNF2-like region to DUF1087 domain were associated with multisystem developmental disorders, while idiopathic epilepsy-related mutations were outside this region. Strong evidence from ClinGen Clinical Validity Framework and evidences from four of the five clinical-genetic aspects suggested an association between CHD4 variants and epilepsy. CONCLUSIONS: CHD4 was potentially a candidate pathogenic gene of childhood idiopathic epilepsy with arrhythmia. The molecular sub-regional effect of CHD4 mutations helped explaining the mechanisms underlying phenotypic variations.

Heterozygous PGM3 Variants Are Associated With Idiopathic Focal Epilepsy With Incomplete Penetrance.

INTRODUCTION: Idiopathic focal epilepsy (IFE) is a group of self-limited epilepsies. The etiology for the majority of the patients with IFE remains elusive. We thus screened disease-causing variants in the patients with IFE. METHODS: Whole-exome sequencing was performed in a cohort of 323 patients with IFE. Protein modeling was performed to predict the effects of missense variants. The genotype-phenotype correlation of the newly defined causative gene was analyzed. RESULTS: Four novel heterozygous variants in PGM3, including two de novo variants, were identified in four unrelated individuals with IFE. The variants included one truncating variant (c.1432C > T/p.Q478X) and three missense variants (c.478C > T/p.P160S, c.1239C > G/p.N413K, and c.1659T > A/p.N553K), which had no allele frequency in the gnomAD database. The missense variants were predicted to be damaging and affect hydrogen bonds with surrounding amino acids. Mutations Q478X, P160S, and N413K were associated with benign childhood epilepsy with centrotemporal electroencephalograph (EEG) spikes. P160S and N413K were located in the inner side of the enzyme active center. Mutation N553K was associated with benign occipital epilepsy with incomplete penetrance, located in the C-terminal of Domain 4. Further analysis demonstrated that previously reported biallelic PGM3 mutations were associated with severe immunodeficiency and/or congenital disorder of glycosylation, commonly accompanied by neurodevelopmental abnormalities, while monoallelic mutations were associated with milder symptoms like IFE. CONCLUSION: The genetic and molecular evidence from the present study implies that the PGM3 variants identified in IFE patients lead to defects of the PGM3 gene, suggesting that the PGM3 gene is potentially associated with epilepsy. The genotype-phenotype relationship of PGM3 mutations suggested a quantitative correlation between genetic impairment and phenotypic severity, which helps explain the mild symptoms and incomplete penetrance in individuals with IFE.

Negative regulation of Toll-like receptor signaling pathway.

TLRs are primary sensors of invading pathogens, recognizing conserved microbial molecules and activating signaling pathways that are pivotal to innate and adaptive immune responses. However, a TLR signaling pathway must be tightly controlled because its excessive activation can contribute to the pathogenesis of many human diseases. This review provides a summary of the different mechanisms that are involved in the negative regulation of TLR signaling pathways.

[Observation on mitosis of Trichomonas vaginalis cultivated in vitro using modified Giemsa staining].

The observation showed that the percentage of Trichomonas vaginalis trophozoites at the stages of interphase, binary fission and multiple fission was 66.5%, 24.1% and 9.4% respectively. Cells in binary fission could be classified as premitotic phase, prophase, metaphase, anaphase and telophase. 3 to 8 microcosms were seen in one trophozoite under multiple fission and the percentage of trophozoites with 3 and 4 microcosms occupied 69% and 24.5% respectively. Cells with abnormal morphs were also observed.

Cyclin G associated kinase interacts with interleukin 12 receptor beta2 and suppresses interleukin 12 induced IFN-gamma production.

Interleukin 12 receptor beta1 (IL-12Rbeta1) and beta2 (IL-12Rbeta2) constitute the functional and high-affinity receptor complex for interleukin 12 (IL-12) and mediate important functions in activated T cells. In this study, we identified cyclin G associated kinase (GAK) as a new IL-12Rbeta2-interacting protein using yeast two-hybrid system and confirmed it by coimmunoprecipitation assays. Overexpression of GAK in activated T cells suppresses IL-12 induced IFN-gamma production but has no detectable effects on its proliferation, whereas knockdown of GAK by RNA interference (RNAi) increases IFN-gamma production. These results suggest that GAK associates with IL-12Rbeta2 and may play a role in regulating IL-12 signaling.

[Study on the geographic information system databases regarding the control of schistosomiasis in Zhongxiang, Hubei province, China].

OBJECTIVE: Using geographic information system (GIS) and the remote sensing techniques (RS), we developed a schistosomiasis database and geographic distribution map in Zhongxiang city,Hubei province in order to display and analyze the endemic situation longitudinally after the water conservancy project is completed. METHODS: Epidemiological data of schistosomiasis and the correlated climate and hydrology data for the last 30 years were collected and the relevant GIS databases were established under Artificial Neural Networks(ANN) and network training of Landsat TM images. RESULTS: GIS database of schistosomiasis in Zhongxiang city, Hubei province and its vicinity areas were developed including 1 maps regarding the epidemic situation of schistosomiasis. The areas of snail distributing were 4.4 hm2, 8.2 hm2, 24 hm2, 130.4 hm2, 8.13 hm2 and 7.53 hm2, respectively. CONCLUSION: The maps created by GIS database and RS techniques supported the complicated query on space and property, providing a new way in keeping,updating and analyzing available data. The techniques used should be able to provide evidence for the control of schistosomiasis to this water conservancy project.

[Observation on moving patterns of Oncomelania snails in rivers and canals].

OBJECTIVE: To understand the moving patterns of Oncomelania snails, intermediate host of S. japonicum, in the water bodies. METHODS: Based on the biological features of the snails, methods and techniques in relation to hydraulics and silt engineering were adopted to investigate the active scrawl ability and passive movement of the snails. RESULTS AND CONCLUSION: The scrawl speed of the snails themselves was very low, 2.45 mm per minute only. The active movement in the water current was therefore almost negligible. The major moving patterns of the snails in rivers and canals were that: 1. Snails adsorbed on different kinds of carriers drifted on the water. 2. Snails suspended on the water and drifted with the current, these were the young snails under 7 weeks of age. Adult snail showed a strong ability of adhesion, 12 times higher than its body weight.