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BackgroundFOXG1-related encephalopathy, also known as FOXG1 syndrome or FOXG1-related disorder, affects most aspects of development and causes microcephaly and brain malformations. This syndrome was previously considered to be the congenital variant of Rett syndrome. The abnormal function or expression of FOXG1, caused by intragenic mutations, microdeletions or microduplications, was considered to be crucial pathological factor for this disorder. Currently, most of the FOXG1-related encephalopathies have been identified in Europeans and North Americans, and relatively few Chinese cases were reported.MethodsArray-Comparative Genomic Hybridization (Array-CGH) and whole-exome sequencing (WES) were carried out for the proband and her parent to detect pathogenic variants.ResultsA de novo nonsense mutation (c.385G>T, p.Glu129Ter) of FOXG1 was identified in a female child in a cohort of 73 Chinese children with neurodevelopmental disorders/intellectual disorders (NDDs/IDs). In order to have a comprehensive view of FOXG1-related encephalopathy in China, relevant published reports were browsed and twelve cases with mutations in FOXG1 or copy number variants (CNVs) involving FOXG1 gene were involved in the analysis eventually. Feeding difficulties, seizures, delayed speech, corpus callosum hypoplasia and underdevelopment of frontal and temporal lobes occurred in almost all cases. Out of the 12 cases, eight patients (66.67%) had single-nucleotide mutations of FOXG1 gene and four patients (33.33%) had CNVs involving FOXG1 (3 microdeletions and 1 microduplication). The expression of FOXG1 could also be potentially disturbed by deletions of several brain-active regulatory elements located in intergenic FOXG1-PRKD1 region. Further analysis indicated that PRKD1 might be a cooperating factor to regulate the expression of FOXG1, MECP2 and CDKL5 to contribute the RTT/RTT-like disorders.DiscussionThis re-analysis would broaden the existed knowledge about the molecular etiology and be helpful for diagnosis, treatment, and gene therapy of FOXG1-related disorders in the future.

David R Powell, Deon D Doree, Christopher M DaCosta, Kenneth A Platt, Gwenn M Hansen, Isaac van Sligtenhorst, Zhi-Ming Ding, Jean-Pierre Revelli, Robert Brommage Lexicon Pharmaceuticals Inc, The Woodlands, TX, 77381, USACorrespondence: David R PowellLexicon Pharmaceuticals Inc., 8800 Technology Forest Place, The Woodlands, TX 77381, USATel +1 281 863 3060Fax +1 281 863 8115Email dpowell@lexpharma.comPurpose: In humans, single nucleotide polymorphisms (SNPs) near the adjacent protein kinase D1 (PRKD1) and G2/M-phase-specific E3 ubiquitin protein ligase (G2E3) genes on chromosome 14 are associated with obesity. To date, no published evidence links inactivation of either gene to changes in body fat. These two genes are also adjacent on mouse chromosome 12. Because obesity genes are highly conserved between humans and mice, we analyzed body fat in adult G2e3 and Prkd1 knockout (KO) mice to determine whether inactivating either gene leads to obesity in mice and, by inference, probably in humans.Methods: The G2e3 and Prkd1 KO lines were generated by gene trapping and by homologous recombination methodologies, respectively. Body fat was measured by DEXA in adult mice fed chow from weaning and by QMR in a separate cohort of mice fed high-fat diet (HFD) from weaning. Glucose homeostasis was evaluated with oral glucose tolerance tests (OGTTs) performed on adult mice fed HFD from weaning.Results: Body fat was increased in multiple cohorts of G2e3 KO mice relative to their wild-type (WT) littermates. When data from all G2e3 KO (n=32) and WT (n=31) mice were compared, KO mice showed increases of 11% in body weight (P< 0.01), 65% in body fat (P< 0.001), 48% in % body fat (P< 0.001), and an insignificant 3% decrease in lean body mass. G2e3 KO mice were also glucose intolerant during an OGTT (P< 0.05). In contrast, Prkd1 KO and WT mice had comparable body fat levels and glucose tolerance.Conclusion: Significant obesity and glucose intolerance were observed in G2e3, but not Prkd1, KO mice. The conservation of obesity genes between mice and humans strongly suggests that the obesity-associated SNPs located near the human G2E3 and PRKD1 genes are linked to variants that decrease the amount of functional human G2E3.Keywords: glucose tolerance, gene trap, homologous recombination, Prkd1, PRKD1, SNP

ABSTRACT Objectives: This study aimed to explore the effects of miR-128b in the regulation of Lipopolysaccharide (LPS) induced apoptosis. Methods: Human Pulmonary Microvascular Endothelial Cells (HPMECs) were transfected with an miR-128b inhibitor and stimulated with LPS for 24 h. FCM was performed to detect apoptosis and Reactive Oxygen Species (ROS) production. In addition, miRNA and caspase-3 expression levels were determined using real-time quantitative polymerase chain reaction and western blotting. Results: LPS significantly induced apoptosis and ROS production and upregulated miR-128b and caspase-3 expressions in HPMECs. However, LPS-induced effects were suppressed when an miR-128b inhibitor was used. Preincu-bation with NAC decreased the LPS-induced apoptosis of HPMECs. Conclusions: These effects were mediated by miR-128b via the caspase-3 pathway.