Search

Introduction: This study was designed to explore the association between the TMEM173 polymorphism (rs7447927) and the severity of enterovirus 71 (EV71) infection among Chinese children. Methods: The TMEM173 polymorphism was identified in EV71‐infected patients (n = 497) and healthy controls (n = 535) using the improved multiplex ligation detection reaction (iMLDR). The interferon‐α (IFN‐α) serum levels were detected using enzyme linked immunosorbent assay (ELISA). Results: The frequencies of the GG genotype and G allele of TMEM173 rs7447927 in the mild EV71 infection and severe EV71 infection groups were markedly higher than those in the control group. The GG genotype and G allele frequencies in severely infected EV71 patients were significantly higher than those in mildly infected EV71 patients. Severely infected EV71 patients with the GG genotype had higher white blood cell counts (WBC), and C‐reactive proteins (CRP), and blood glucose (BG) levels, longer fever duration, higher vomiting frequency, spirit changes, and electroencephalography (EEG) abnormalities. IFN‐α serum concentration in severely infected patients was significantly higher than in the mildly infected group. The IFN‐α concentration in the GG genotype was significantly higher compared with those in the GC and CC genotypes in severe cases. Conclusions: The TMEM173 rs7447927 polymorphism was associated with EV71 infection susceptibility and severity. The G allele and GG genotype are susceptibility factors in the development of severe EV71 infection in Chinese children. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to explore the association between the IRAK4 polymorphism rs4251545 and the severity of enterovirus 71 (EV71) infection in Chinese children. Methods: We analyzed the IRAK4 polymorphism rs4251545 in 617 EV71‐infected patients and 410 controls using the improved multiplex ligation detection reaction. IRAK4 mRNA expression was tested by qRT‐PCR. Serum concentrations of IL‐6 and NF‐κB were detected using ELISA. Results: The frequencies of the GA + AA genotype and A allele in the mild EV71 infection group and in the severe EV71 infection group were significantly higher than those in the normal control group. The frequency of the GA + AA genotype and A allele in severely infected EV71 patients was markedly higher than that in mildly infected EV71 patients. IRAK4 mRNA expression in mildly infected EV71 patients and severely infected patients was significantly higher than that in the control group. IRAK4 mRNA expression in GA + AA genotypes in both mild and severe EV71 infection groups was significantly higher than that in patients with the GG genotype. IL‐6 concentration and the ratio of IL‐6/NF‐κB in severe EV71 cases were significantly lower in patients with the GA + AA genotype than in those with the GG genotype. The ratio of IL‐6/NF‐κB was distinctly higher in severely infected EV71 patients than in mildly infected and control subjects. Conclusions: The IRAK4 polymorphism rs4251545 was associated with the susceptibility and severity of EV71 infection. The A allele is a susceptible factor in the development of severe EV71 infection in Chinese children. [ABSTRACT FROM AUTHOR]

Pitt-Hopkins syndrome (PTHS), belonging to the group of 18q-syndromes, is a rare genetic disorder caused by mutations in TCF4. PTHS is characterized by distinctive facial appearance, intermittent hyperventilation, intellectual disability and developmental delay. Although patients with PTHS generally have various systemic symptoms, most of them with a TCF4 mutation manifest the central nervous system (CNS) disorders. We described the first Chinese case with Pitt-Hopkins syndrome based on clinical presentations and genetic findings. In addition to the typical features of PTHS, the girl also had paroxysms of tachypnea followed by cyanosis and recurrent seizures. Comprehensive medical examinations were performed including metabolic screening, hepatic and renal function evaluation, abdominal and cardiac ultrasounds. The presence of epileptic discharges in electroencephalography and abnormal brain magnetic resonance imaging were found. High-throughput sequencing was used to detect genetic mutations associated with CNS disorders. Sanger sequencing was used to confirm the mutations in the patient. The c.2182C＞T (p.Arg728Ter) mutation was a de novo nonsense mutation at exon 18 in the TCF4 gene of the patient. In conclusion, we have identified a de novo nonsense mutation of TCF4 carried by a Chinese girl with PTHS. The patient underwent anti-epileptic therapy (sodium valproate, levetiracetam, clonazepam), resulting in a reduction of the seizures. [ABSTRACT FROM AUTHOR]

Background Oligoadenylate synthetase 3 (OAS3) is interferon-induced antiviral enzyme, playing a significant role in the innate immune response. Genetic polymorphism in OAS3 gene has been reported to be a susceptibility factor in many infected diseases, but evidence of its effect on enterovirus 71 (EV71) infection is still lacking. Objectives An attempt study was made to investigate whether genetic polymorphism of OAS3 S381R is associated with the severity of EV71 infection in Chinese children. Study design Retrospectively sumed up the clinical onsets and experimental results for 249 cases with EV71 infection (including 151 mild cases and 98 severe cases) and 243 controls. An improved multiplex ligation detection reaction (iMLDR) technique was carried out to analyze polymorphism in OAS3 S381R G/C gene for genetic association analyses. The plasma levels of IFN-γ were determined by enzyme-linked immunosorbent assays. Results The distribution of OAS3 S381R CC genotype (73.47%) and C allele (85.20%) in severe cases was markedly higher than in mild cases (45.70%, P < .01; 67.88%, P < .01). The blood IFN-γ levels of severe cases were significantly lower in CC genotype (131.66 ± 10.84 pg/mL) compared to GG (183.37 ± 24.50 pg/mL, p < .01) and GC genotype (168.48 ± 26.57 pg/mL, p < .01). Conclusions Carrying the C allele of the OAS3 S381R gene could be a susceptibility factor in the development of severe EV71 infection in Chinese children. [ABSTRACT FROM AUTHOR]

The tumor microenvironment (TME) is connected to immunotherapy responses, but it remains unclear how cancer cells and host tissues differentially influence the immune composition within TME. Here, we performed single-cell analyses for autologous samples from liver metastasized colorectal cancer to disentangle factors shaping TME. By aligning CD45+ cells across different tissues, we classified exhausted CD8+ T cells (Texs) and activated regulatory T cells as M-type, whose phenotypes were associated with the malignancy, while natural killer and mucosal-associated invariant T cells were defined as N-type, whose phenotypes were associated with the niche. T cell receptor sharing between Texs in primary and metastatic tumors implicated the presence of common peripheral non-exhausted precursors. For myeloid cells, a subset of dendritic cells (DC3s) and SPP1 + macrophages were M-type, and the latter were predominant in liver metastasis, indicating its pro-metastasis role. Our analyses bridge immune phenotypes of primary and metastatic tumors, thereby helping to understand the tumor-specific contexture and identify the pro-metastasis components. [Display omitted] • Immune cell phenotypic linkage with colorectal cancer and liver metastasis depicted • Malignancy-associated exhausted and regulatory T cells show diverse TCR dependency • SPP1 + TAMs are malignancy associated and are linked to liver metastasis • DCs are mainly associated with host organ except a malignancy-associated DC3 subset Liu et al. reveal the roles of malignancy and host-organ contexture in shaping immune infiltrates within a tumor microenvironment based on single-cell phenotypic alignment of colorectal cancer and the autologous liver metastasis [ABSTRACT FROM AUTHOR]

Liver metastasis is associated with immunotherapy resistance, although the underlying mechanisms remain incompletely understood. By applying single cell RNA‐sequencing to a concurrent subcutaneous and liver tumor murine model to recapitulate liver metastases, it is identified that subsets within tumor‐infiltrating exhausted CD8+ T (Tex) cells and immunosuppressive tumor‐associated macrophages (TAMs) display opposite responses to concurrent liver tumors and anti‐PD‐1 treatment, suggesting a complex immune regulating network. Both angiogenic and interferon‐reactive TAMs show increased frequencies in implanted liver tumors, and anti‐PD‐1 treatment further elevates the frequencies of angiogenic TAMs. Such TAMs frequencies negatively correlate with the proportions of cytotoxic T cell subsets. Further, expression of interferon‐stimulated genes in TAMs is dramatically reduced under effective anti‐PD‐1 treatment, while such tendencies are diminished in mice with implanted liver tumors. Therefore, the study indicates that liver metastases could increase immunosuppressive TAMs frequencies and inhibit Tex responses to PD‐1 blockade, resulting in compromised systemic antitumor immunity and limited immunotherapy efficacy. [ABSTRACT FROM AUTHOR]

• Most rat cerebrovascular pericytes are α-SMA positive. • CYP4A and α-SMA coexpress in rat cerebral VSMCs and most pericytes. • 20-HETE is positively correlated with cerebral mural cell contractility. • 20-HETE promotes the myogenic response of rat parenchymal arterioles. • 20-HETE enhances CBF autoregulation in rat surface and deep cortex. We previously reported that deficiency in 20-HETE or CYP4A impaired the myogenic response and autoregulation of cerebral blood flow (CBF) in rats. The present study demonstrated that CYP4A was coexpressed with alpha-smooth muscle actin (α-SMA) in vascular smooth muscle cells (VSMCs) and most pericytes along parenchymal arteries (PAs) isolated from SD rats. Cell contractile capabilities of cerebral VSMCs and pericytes were reduced with a 20-HETE synthesis inhibitor, HET0016, but restored with 20-HETE analog WIT003. Similarly, intact myogenic responses of the middle cerebral artery and PA of SD rats decreased with HET0016 and were rescued by WIT003. The myogenic response of the PA was abolished in SS and was restored in SS.BN5 and SS. Cyp4a1 rats. HET0016 enhanced CBF and impaired its autoregulation in the surface and deep cortex of SD rats. These results demonstrate that 20-HETE has a direct effect on cerebral mural cell contractility that may play an essential role in controlling cerebral vascular function. [ABSTRACT FROM AUTHOR]

R1636 --> 20‐HETE is a metabolite of arachidonic acid produced by enzymes of CYP4A and CYP4F families. We previously reported that Dahl S rats have a genetic deficiency in the production of 20‐HETE and the expression of CYP4A enzymes and exhibit impaired myogenic response of the middle cerebral artery (MCA) and autoregulation of cerebral blood flow (CBF) but the mechanism is unknown. The present study explored whether 20‐HETE has direct effects on the regulation of cerebral mural cell contractility that may play an essential role in autoregulation of CBF in the surface and deep cortex. We found that CYP4A was expressed in vascular smooth muscle cells (VSMCs) and pericytes along parenchymal arteries and capillaries isolated from the MCA territory of SD rats. Gel size was reduced to a lesser extent in VSMCs treated with the 20‐HETE synthesis inhibitor, HET0016 (10 μM) versus vehicle (17.9 ± 0.5 % vs. 28.3 ± 0.5 %; n = 9), indicating loss of contractility. Similarly, constriction of cerebral pericytes treated with HET0016 was reduced relative to controls. Cell contractile capability of cerebral VSMC and pericyte collaboratively play a role in regulating CBF in the superficial and deep cortex of the brain by modulation of the myogenic response of the MCA and arterioles, respectively. CBF was well autoregulated in the surface and deep cortex in SD rats and only increased by 12.9 ± 1.7 % and 13.3 ± 1.9 %, respectively, when pressure was elevated from 100 to 140 mmHg. In contrast, CBF increased by 34.6 ± 3.2 % and 28.5 ± 2.3 %, respectively after the rats were given HET0016 (2 mg/kg). These results demonstrate that CYP4A is expressed both in VSMC and pericytes of parenchymal arteries and capillaries, that blockade of 20‐HETE reduces the contractile activity of these cells and attenuates autoregulation of CBF in the superficial and deep cortex of the brain. They provide novel insight into human genetic studies indicating that inactivate variants of 20‐HETE producing enzymes are associated with a higher incidence of hypertension, stroke, and AD. [ABSTRACT FROM AUTHOR]

Ischemic stroke is one of the most disabling diseases and a leading cause of death globally. Despite advances in medical care, the global burden of stroke continues to grow, as no effective treatments to limit or reverse ischemic injury to the brain are available. However, recent preclinical findings have revealed the potential role of transient receptor potential cation 6 (TRPC6) channels as endogenous protectors of neuronal tissue. Activating TRPC6 in various cerebral ischemia models has been found to prevent neuronal death, whereas blocking TRPC6 enhances sensitivity to ischemia. Evidence has shown that Ca2+ influx through TRPC6 activates the cAMP (adenosine 3',5'-cyclic monophosphate) response element-binding protein (CREB), an important transcription factor linked to neuronal survival. Additionally, TRPC6 activation may counter excitotoxic damage resulting from glutamate release by attenuating the activity of N-methyl-d-aspartate (NMDA) receptors of neurons by posttranslational means. Unresolved though, are the roles of TRPC6 channels in non-neuronal cells, such as astrocytes and endothelial cells. Moreover, TRPC6 channels may have detrimental effects on the blood–brain barrier, although their exact role in neurovascular coupling requires further investigation. This review discusses evidence-based cell-specific aspects of TRPC6 in the brain to assess the potential targets for ischemic stroke management. [ABSTRACT FROM AUTHOR]

Coffin-Siris syndrome (CSS) (OMIM #135900) involves multiple congenital malformations, including hypotonia, short stature, sparse scalp hair, a coarse face, prominent eyebrows, a wide mouth, delayed bone age, and hypoplastic or absent fifth fingers/toes or nails, together with developmental delay. The cause of CSS is suggested to be related to alterations in the BRG- or HRBM-associated factor (BAF) pathway in humans. In this gene family, pathogenic variations in the AT-rich interactive domain-containing protein 1B (ARID1B) gene are revealed to be a significant element causing neurodevelopmental disability in patients with CSS. Herein, we describe the clinical features and gene variations in four Chinese patients with CSS. All the patients shared common features of short fifth fingers/toes or hypoplastic nails, coarse facial features, thick eyebrows, long cilia, a flat nasal bridge, a broad nose, a wide mouth, a high palate, and hypotonia. Besides, they had an intellectual disability, language, and motor developmental delay. Candidate genes were screened for variations using polymerase chain reaction (PCR) and sequencing. The variations were sequenced by next-generation sequencing and confirmed by first-generation sequencing. Exome sequencing suggested four de novo variations in the ARID1B gene in four unrelated patients. These included two frameshift variations (c.3581delC, c.6661_6662insG) and two nonsense variations (c.1936C>T, c.2248C>T). Of the four variations, three variations were novel. The results in our present study broaden the understanding of the disease and further interpret the molecular genetic mechanism of these rare variations in CSS. [ABSTRACT FROM AUTHOR]

R1943 --> We recently reported that cerebral vascular dysfunction precedes cognitive impairment in TgF344‐AD (AD) rat model of Alzheimer's disease. However, whether abnormalities in cerebral vascular smooth muscle cells (VSMCs) play a direct role has not been studied. In the present study, we first confirmed that the AD rats started to develop learning and memory deficits at 24‐week of age using an eight‐arm water maze. AD rats (n = 11) took a longer time to escape and displayed more errors than age‐matched wildtype (WT) rats (n = 6). We also completed a longitudinal comparison of the myogenic response (MR) of the middle cerebral artery (MCA) and found that the MR was similar in AD and WT rats at 8‐ to 12‐week of age when perfusion pressure was increased from 40 to 180 mmHg. However, the MR started first became significantly reduced in 16‐week old AD rats (n = 6) as the inner diameter of the MCA only decreased by 8.2 ± 2.4% when perfusion pressure was increased from 40 to 180 mmHg compared with 14.5% ± 2.0% in age‐matched WT rats (n = 6). The impaired MR of the MCA was exacerbated in AD rats with aging. Consistent with the exvivo MR studies, in vivo experiment using a laser‐Doppler flowmeter demonstrated that the cerebral blood flow (CBF) autoregulation of AD rats (n = 4) was impaired in the surface and deep cortex at 24‐week of age compared to age‐matched WT rats (n = 4). Furthermore, we found an endogenous reduced cell contractile capability in the cerebral VSMCs isolated from AD (n = 4) compared with WT rats (n = 4), detected by a maximal gel size reduction by 15.7 ± 0.9% vs. 25.4 ± 1.0% using a collagen gel‐based assay kit. These results provide evidence that cerebral VSMC dysfunction, impaired MR and autoregulation of CBF correlates, which precedes the development of memory and learning deficits in the TgF344‐AD rats. However, the underlying mechanisms causing the loss of VSMCs contractility in this AD model expressing mutant human amyloid precursor protein (APPsw) and presenilin 1 (PS1ΔE9) genes remains to be determined. Nevertheless, these results provide novel insight into vascular contribution to AD, which will lay the foundation for the discovery of new biomarkers in AD. [ABSTRACT FROM AUTHOR]

Polycystic kidney disease with Tuberous sclerosis is a disease caused by the deletions of the TSC2‐PKD1 gene. The disease is rarely reported and the characterized manifestation is severe polycystic kidney growth. The diagnosis can be made by molecular analysis. We report the first case of PKDTS discovered in infancy in China with typical neurological and renal manifestations. The patient has infantile spasm, polycystic kidney, skin damage, hypertension, and hematuria after infection. After effective treatment of Rapamycin, the seizures were completely controlled. There was not been any renal function damage in the patient. At the same time, we review the related literature and further elaborate on the variety of clinical manifestations, treatment, and prognosis. [ABSTRACT FROM AUTHOR]

Purpose: To identify the causative variants in two unrelated Chinese patients presenting with epilepsy and deafness. Methods: The two patients underwent a thorough examination, including brain MRI, EEG and metabolic studies. Next‐generation sequencing (NGS) was performed on genomic DNA samples from the siblings and parents. Sanger sequencing was used to confirm the variants. Results: Gene sequencing revealed that they carried two novel compound heterozygous missense variants of the TBC1D24: c.116 C > T (p.Ala39Val) and c.827 T > C (p.Ile276Thr) in patient 1; c.404 C > T (p.Pro135Leu) and c.679 T > C (p.Arg227Trp) in patient 2. Audiologic examination showed bilateral sensorineural hearing loss in both patients. Conclusion: We have found novel variants in the TBC1D24 in two Chinese unrelated patients. They result in a rare phenotype, characterized by drug‐resistant epilepsy and deafness. [ABSTRACT FROM AUTHOR]

Recently, we reported a mutation in γ-adducin (ADD3) was associated with an impaired myogenic response of the afferent arteriole and hypertension-induced chronic kidney disease (CKD) in fawn hooded hypertensive (FHH) rats. However, the mechanisms by which altered renal blood flow (RBF) autoregulation promotes hypertension-induced renal injury remain to be determined. The present study compared the time course of changes in renal hemodynamics and the progression of CKD during the development of DOCA-salt hypertension in FHH 1BN congenic rats [wild-type (WT)] with an intact myogenic response versus FHH 1BN Add3KO (Add3KO) rats, which have impaired myogenic response. RBF was well autoregulated in WT rats but not in Add3KO rats. Glomerular capillary pressure rose by 6 versus 14 mmHg in WT versus Add3KO rats when blood pressure increased from 100 to 150 mmHg. After 1 wk of hypertension, glomerular filtration rate increased by 38% and glomerular nephrin expression decreased by 20% in Add3KO rats. Neither were altered in WT rats. Proteinuria doubled in WT rats versus a sixfold increase in Add3KO rats. The degree of renal injury was greater in Add3KO than WT rats after 3 wk of hypertension. RBF, glomerular filtration rate, and glomerular capillary pressure were lower by 20%, 28%, and 19% in Add3KO rats than in WT rats, which was associated with glomerular matrix expansion and loss of capillary filtration area. The results indicated that impaired RBF autoregulation and eutrophic remodeling of preglomerular arterioles increase the transmission of pressure to glomeruli, which induces podocyte loss and accelerates the progression of CKD in hypertensive Add3KO rats. [ABSTRACT FROM AUTHOR]

We recently reported that KO of Dual‐specificity protein phosphatase 5 (Dusp5) enhances myogenic reactivity and blood flow autoregulation in the cerebral and renal circulations in association with increased levels of pPKC and pERK1/2 in the cerebral and renal arteries and arterioles. In the kidney, hypertension‐related renal damage was significantly attenuated in Dusp5 KO rats. Elevations in pPKC and pERK1/2 promote calcium influx in VSMC and facilitate vasoconstriction. However, whether DUSP5 plays a role in altering the passive mechanical properties of cerebral and renal arterioles has never been investigated. In this study, we found that KO of Dusp5 did not alter body weights, kidney and brain weights, plasma glucose, and HbA1C levels. The expression of pERK is higher in the nucleus of primary VSMC isolated from Dusp5 KO rats. Dusp5 KO rats exhibited eutrophic vascular hypotrophy with smaller intracerebral parenchymal arterioles and renal interlobular arterioles without changing the wall‐to‐lumen ratios. These arterioles from Dusp5 KO rats displayed higher myogenic tones, better distensibility, greater compliance, and less stiffness compared with arterioles from WT control rats. VSMC of Dusp5 KO rats exhibited a stronger contractile capability. These results demonstrate, for the first time, that DUSP5 contributes to the regulation of the passive mechanical properties of cerebral and renal arterioles and provide new insights into the role of DUSP5 in vascular function, cancer, stroke, and other cardiovascular diseases. [ABSTRACT FROM AUTHOR]

• TH deficiency is an autosomal recessive inborn error of dopamine transmission, which the deficient gene is at the chromosome 11. • TH deficiency leads to developmental delay, infantile parkinsonism and encephalopathy. • We report three TH deficiency patients. After L-DOPA treatment, their condition had improvement. Tyrosine hydroxylase (TH) deficiency is a rare autosomal recessive inborn error of dopamine transmission, which the deficient gene is at the chromosome 11, also called'Segawa Syndrome'. TH converts tyrosine into L-DOPA, which is the direct precursor of catecholamine biosynthesis. TH deficiency causes a neurological disease with primary extrapyramidal signs and a variable response to L-DOPA. We report three patients in China who were diagnosed with Tyrosine hydroxylase (TH) deficiency by genetic testing and clinical manifestations. After L-DOPA treatment, their condition had sustained improvement. [ABSTRACT FROM AUTHOR]

Cohen syndrome is a rare, genetic, connective-tissue disorder, which is caused by mutations in the gene COH1 (VPS13B, Vacuolar Protein Sorting 13 Homolog B) at the chromosome 8q22. The disease is rare reported, which major clinical features include postnatal microcephaly, obesity, short stature, intellectual disability, progressive retinal dystrophy, intermittent neutropenia and many other unusual facial feature. We report four patients in China who were diagnosed with Cohen syndrome by genetic testing and clinical manifestations. At the same time, we review the related literature, and further expound the molecular mechanism of the disease, a variety of clinical manifestations, treatment and prognosis. [ABSTRACT FROM AUTHOR]

Enterovirus 71 (EV71) is a single-strand RNA virus that causes hand, foot and mouth disease (HFMD) in infants and young children, leading to neurological complications with significant morbidity and mortality. Unfortunately, the pathogenesis of EV71 infection is not well understood. In this study, we investigated the IL-17F rs1889570 and rs4715290 gene polymorphisms in a Chinese Han population. Severe cases and cases with EV71 encephalitis had a significantly higher frequency of the rs1889570 T/T genotype and T allele. The serum IL-17F levels in rs1889570 T/T and C/T genotypes were also significantly elevated when compared to C/C genotypes. However, there was no significant difference observed in rs4715290 genotype distribution and allele frequency. These findings suggest that IL-17F rs1889570 gene polymorphisms are significantly associated with the susceptibility to severe EV71 infection in Chinese Han children. [ABSTRACT FROM AUTHOR]

The 2'5'-oligoadenylate synthetase (OAS) is an interferon (IFN)-induced protein that plays an important role in the antiviral action of IFN, with OAS3 being one of the four OAS classes (OAS1, OAS2, OAS3, OASL). The effect of OAS on several infectious viral diseases has been reported; however, a study of the effect of OAS3 on enterovirus 71 (EV71) is lacking. The purpose of this study was to evaluate the association of the OAS3 rs1859330 G/A genetic polymorphism with susceptibility and severity of EV71 infection. We investigated 370 Chinese Han children with hand-foot-mouth disease (HFMD) (214 of which were mild cases while 156 were severe). An improved multiplex ligation detection reaction (iMLDR) technique was carried out to examine the genotype. The AA genotype distribution (p = 0.002) and A allele frequency (OR = 1.83, 95% CI 1.32-2.52, p < 0.001) of OAS3 rs1859330 in severe cases were significantly higher than in mild cases. When comparing the different genotypes in EV71-infected patients, there were statistical differences in relation to rash (p = 0.03), oral ulcers (p = 0.005), pathologic reflex (p = 0.003), WBC counts (p = 0.032), CRP (p = 0.024), BG concentrations (p = 0.029), ALT (p = 0.02), and EEG (p = 0.019). However, there were no differences in relation to age, gender, AST, CK-MB, CT/ MRI, as well as some symptoms and signs (e.g. duration of fever (days), headache, convulsions, consciousness disturbance, paralysis, sign of meningeal irritation). In the cerebrospinal fluid (CSF) of severe cases, there were no differences in the levels of white cells, protein, glucose, chloride, lymphocytes and monocytes between the different genotypes. The plasma levels of IFN-γ in EV71-infected patients were significantly higher than in the control group (p < 0.01). IFN-γ concentrations in severe cases were lower in A allele carriers (AA+GA) (118.5 ± 12.6pg/mL) than in GG homozygotes (152.6 ± 56.3pg/mL p < 0.05). These findings suggest that the OAS3 rs1859330 G/A genetic polymorphism is associated with the severity of EV-71 infection, and that the A allele is a risk factor for the development of severe EV71 infection. [ABSTRACT FROM AUTHOR]

Highlights • Missense mutations in ATP6 gene were commn causes of mitochondrial encephalomyopathies. • We found a novel missense mutation in ATP6 gene (m.8914C>T) associated with mitochondrial encephalomyopathy. • The mutation load in blood sample of patient is 59.49%. • Activity of complexes in blood was normal, but the function of mitochondrial oxidative phosphorylation was declined. • The m.8914C>T in ATP6 gene was related with dysfunction of complexV. Abstract Mutations in ATP6 gene are frequent causes of mitochondrial encephalomyopathies. ATP6 gene encodes one subunit of complexⅤ. The present study described a missense mutation in ATP6 gene in a 8-year-old Chinese boy with mitochondrial encephalomyopathy. We identified one missense mutation in ATP6 gene (m.8914C>T) by mitochondrial DNA sequencing. This mutation altered the amino acid proline in serine, and alterative protein is predicted to be harmful. The mutation load in blood sample of patient is 59.49%. Activity of all mitochondrial complexes in blood are normal, however, the total function of mitochondrial oxidative phosphorylation were declined (including pathwayⅠ, pathwayⅡ and pathwayⅣ). The missense mutation (m.8914C>T) in ATP6 gene could result in abnormal function of complexV and is related with mitochondrial encephalomyopathy. [ABSTRACT FROM AUTHOR]