A novel hemizygous CD40L mutation of X-linked hyper IgM syndromes and compound heterozygous DOCK8 mutations of hyper IgE syndromes in two Chinese families.

X-linked hyper-immunoglobulin M (X-HIGM) syndrome and autosomal recessive hyper-immunoglobulin E syndrome (HIES) are rare inborn errors of immunity characterized by recurrent infections due to immune system impairment. In this study, we identified a novel hemizygous CD40 ligand (CD40L) mutation and compound heterozygous dedicator of cytokinesis-8 (DOCK8) mutations in two Han Chinese families with X-HIGM and HIES, respectively. We aimed to investigate the association between their genotypes and phenotypes. Genomic DNA was extracted from peripheral blood samples obtained from the families. Whole exome sequencing and Sanger sequencing were performed to identify and verify pathogenic variants in the two families. Clinical analyses of the probands were also performed. A novel hemizygous mutation of CD40L in exon 2 (c.257delA) was identified in the first proband, resulting in the substitution of glycine with glutamic acid at codon 86 of the protein. This leads to premature termination of translation at downstream codon 9 (p.E86Gfs*9). Sanger sequencing confirmed that the variant was inherited from the mother. The second proband carried two novel compound heterozygous mutations in DOCK8: one at exon 14 (c.1546C > G) inherited from the father, and the other at intron 41 (c.5355 + 6C > T; splicing) inherited from the mother. This study enhances our understanding of the pathogenetic mutation spectrum of CD40L and DOCK8 genes, facilitating the prenatal diagnosis of X-HIGM and HIES and enabling timely treatment of patients.

[Clinical features of children with Epstein-Barr virus-related acute liver failure: an analysis of four cases].

A retrospective analysis was performed for the clinical data of four children with Epstein-Barr virus (EBV)-related acute liver failure. There were two boys and two girls with a median age of 10 months (range 8.5-44 months). Of the four children, three were diagnosed with infectious mononucleosis (IM), among whom two met the diagnostic criteria of hemophagocytic lymphohistiocytosis (HLH), and one was diagnosed with past EBV infection. All the children had positive EBV DNA in blood and all had pyrexia, hepatomegaly, and jaundice on admission. Three children had the symptom of splenomegaly, ascites, or vomiting. Two children had enlargement of cervical lymph nodes, skin rash, or pleural effusion. One child had gastrointestinal bleeding or stage 2 hepatic encephalopathy. All the children had an abnormal lymphocyte count of <10%, and only one child had leukocytosis and thrombocytopenia. Among the four children, alanine aminotransferase level increased by 10-100 times; total bilirubin level increased by 3-5 times; lactate dehydrogenase level increased by many 10 times; prothrombin time prolonged significantly. All the children were given antiviral therapy with intravenously injected acyclovir or ganciclovir, as well as hepatocyte growth factor to promote hepatocyte growth and hormone to alleviate inflammatory response. Two children were given plasma exchange in addition, among whom one was given the combination of continuous venovenous hemodiafiltration. Two children with HLH were given chemotherapy according to the HLH-2004 regimen. Three children survived, and one child with HLH died of multiple organ failure. It is concluded that EBV infection can cause acute liver failure and that early use of multimodality therapy including blood purification may be beneficial for prognosis in these children.

[Association between S100B gene polymorphisms and hand, foot and mouth disease caused by enterovirus 71 infection].

OBJECTIVE: To investigate the association between rs9722 polymorphisms in the S100B gene and hand, foot and mouth disease (HFMD) caused by enterovirus 71. METHODS: A total of 124 HFMD children with enterovirus 71 infection were enrolled as subjects, and 56 healthy children were enrolled as control group. The rs9722 polymorphisms in the S100B gene were detected for both groups, and the serum level of S100B protein was measured for 74 HFMD children. RESULTS: The rs9722 locus of the S100B gene had three genotypes, CC, CT, and TT, and the genotype frequencies were in accordance with Hardy-Weinberg equilibrium. Compared with the control group, the HFMD group had significant increases in the frequencies of TT genotype and T allele (P<0.01). Children with severe HFMD caused by enterovirus 71 infection had significantly higher frequencies of TT genotype and T allele than those with moderate or mild HFMD (P<0.05). Compared with the cured patients, the patients with poor prognosis had significant increases in the frequencies of TT genotype and T allele in the rs9722 locus of the S100B gene (P<0.05). Among the 74 children with HFMD, the children with TT genotype had the highest serum level of S100B protein, and those with CC genotype had the lowest level (P<0.01). CONCLUSIONS: T allele in the rs9722 locus of the S100B gene might be a risk factor for severe HFMD caused by enterovirus 71 infection.

[Clinical characteristics and prognostic factors of children with critical hand-foot-mouth disease treated with mechanical ventilation].

OBJECTIVE: To investigate the clinical characteristics of children with critical hand-foot-mouth disease (HFMD) who were treated with mechanical ventilation and to explore the risk factors for poor prognosis. METHODS: The clinical data of 63 children with critical HFMD who were admitted to the pediatric intensive care unit between April 2012 and September 2013 and needed mechanical ventilation were retrospectively analyzed. RESULTS: Among the 63 children, 43 were boys and 20 were girls, and their mean age was 25 ± 18 months, with 81% under 3 years old. The four death cases were all under three years old. Compared with the cured cases, the death cases had a significantly lower mean age (8 ± 3 months vs 25 ± 18 months; P<0.05). Poor peripheral circulation above the elbow or knee joint, pulmonary edema involving at least two thirds of the lung field, and pulmonary hemorrhage were all closely related to death (P<0.01). The death cases and cured cases had significantly different peripheral white blood cell counts, blood lactic acid, and blood glucose (24 ± 11× 109/L vs 12 ± 5×109/L; 6.6 ± 1.8 mmol/L vs 3.6 ± 1.7 mmol/L; 16.4 ± 2.5 mmol/L vs 10.0 ± 3.0 mmol/L). The cases with critical illness score <90 had a significantly higher death risk (P<0.01). CONCLUSIONS: Children with critical HFMD are mainly under 3 years old. The children face extremely high risk of death when they suffer from poor peripheral circulation above the elbow or knee joint, pulmonary edema involving at least two thirds of the lung field, and pulmonary hemorrhage. Significant increases in peripheral white blood cell counts, blood lactic acid, and blood glucose are risk factors for poor prognosis. Critical illness score is also related to poor prognosis.

MiR-19a Promotes Migration And Invasion By Targeting RHOB In Osteosarcoma.

INTRODUCTION: Osteosarcoma is the most common bone tumor with high metastasis and recurrence rate. MicroRNA-19a (miR-19a) has been reported to act as tumor oncogene in multiple cancers. The objective of the study was to explore the molecular mechanisms of miR-19a in osteosarcoma cell migration and invasion. MATERIALS AND METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting were employed to measure the levels of miR-19a and RhoB in osteosarcoma tissues and cell lines. Transwell assay was employed to analyze the tissues and cell lines' migratory and invasive abilities. Dual luciferase reporter assay was utilized to analyze the association between miR-19a and RhoB. RESULTS: MiR-19a was overexpressed in osteosarcoma tissues and cell lines. MiR-19a promoted osteosarcoma cell migration and invasion in vitro. RhoB was thus confirmed as a direct and functional target of miR-19a, and it could partially reverse the function of miR-19a. Knockdown miR-19a inhibited osteosarcoma cell epithelial-mesenchymal transition (EMT) and suppressed osteosarcoma xenograft growth. CONCLUSION: MiR-19a enhanced cell migration, invasion and EMT through RhoB in osteosarcoma. The newly identified miR-19a/RhoB axis provides novel insight into the progression of osteosarcoma and offers a promising target for osteosarcoma therapy.