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OBJECTIVE: To collect the clinical features and gene mutation types of children with neuronal ceroid lipofuscinosis(NCLs)in China,and to help to make genetic diagnosis of NCLs patients. METHODS: The clinical manifestations and examinations of one case with complaints of language disorder for 1.5 years,dyskinesia for 0.5 years and repeated convulsions for one week were collected,and literatures of NCLs from China were reviewed. RESULTS: The electroencephalogram(EEG)showed multiple spikes and slow-wave discharges bilaterally. The brain MRI scan showed high hyperintensities adjacent to the bilateral posterior horns of the lateral ventricles on T2-weighted images and broadened cerebellar fissures. The "leukoencephalopathies and symptomatic epilepsy" was diagnosed. The genetic analysis showed that the proband had a homozygous missense point mutation c.892 G>A(p.Glu298 Lys)(reference sequence:NM＿017882.2)in exon 7 of CLN6 and that both his parents were heterozygous for the mutation. The diagnosis of late infantile neuronal ceroid lipofuscinosis(LINCLs)was confirmed according to the clinical features and genetic analysis results. In CNKI,WANFANG and WIPP Databases,we reviewed the relevant domestic reports about NCLs(28 articles). A total of 3 cases of CLN6 gene mutation were reported,including 2 cases of LINCLs caused by heterozygous mutation and 1 case of JNCLs caused by homozygous mutation. Here we reported the first case of LINCLs caused by a CLN6 homozygous mutation in China. CONCLUSION: This is the first case of LINCLs caused by CLN6 homozygous mutation reported in China. Our report expands the genotype data for NCLs.The mutant genes reported in NCLs patients are CLN1,CLN2,CLN3,CLN5,CLN6 and CLN7,and the clinical manifestations are intractable epilepsy,decreased vision,decreased intelligence,mental and motor dysfunction,personality and behavior changes,and memory decline. A gene sequencing panel for investigating unexplained seizures,leukoencephalopathies and inherited metabolic disorder can help to make the diagnosis.
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Autism spectrum disorder (ASD) is a kind of neurodevelopmental multigenic disorder. More than one hundred of candidate genes for ASD have been reported. The candidate gene research for ASD involves in chromosome loci and screening of candidate genes and epigenetic abnormalities for candidate genes. The reported genes encode neural adhesion molecules, ion channels, scaffold proteins, protein kinases, receptor protein and carrier protein, signaling modulate molecules and circadian relevant proteins. The research of mutation screening and expression regulation of candidate genes can help to elucidate genetic mechanisms for ASD, and may provide new approaches for the diagnosis and treatment of this disorder. This article reviews the research advance in candidate genes for ASD.
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Humans , Autism Spectrum Disorder , Genetics , Gene Dosage , Genetic Predisposition to Disease , Ion Channels , Genetics , Nerve Tissue Proteins , Genetics , Signal Transduction , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To study serum concentration and mRNA expression of interleukin-13 (IL-13) in children with steroid-responsive nephrotic syndrome (SRNS) and the effect of methylprednisolone pulse therapy (MPT) on IL-13 expression.</p><p><b>METHODS</b>Twenty-eight children with SRNS were enrolled in this study. Serum protein level of IL-13 was measured using ELISA and IL-13 mRNA expression in peripheral blood mononuclear cells (PBMC) was detected with RT-PCR before MPT, 2 and 5 days after MPT, and 2 weeks after disappearance of proteinuria following MPT. Twenty-four urinary protein was measured with the biuret assay. Twenty healthy children were used as controls.</p><p><b>RESULTS</b>Serum IL-13 levels (38.48 +/- 13.01 pg/mL vs 5.18 +/- 2.71 pg/mL) and PBMC IL-13 mRNA expression (1.31 +/- 0.23 vs 0.36 +/- 0.07) before MPT in SRNS patients were significantly higher than in the controls. After 5 days of MPT and 2 weeks after disappearance of proteinuria following MPT, serum IL-13 levels (15.33 +/- 7.81 and 5.35 +/- 2.12 pg/mL respectively) and PBMC IL-13 mRNA expression (0.89 +/- 0.26 and 0.33 +/- 0.08 respectively) were significantly reduced (P < 0.01). Serum IL-13 levels and PBMC IL-13 mRNA expression in SRNS patients 2 weeks after disappearance of proteinuria following MPT were reduced to control levels, but remained at a higher level than controls 5 days after MPT. A positive correlation was found between serum levels of IL-13 and 24-hour urinary protein in SRNS patients before (r=0.75, P < 0.01) and after 2 and 5 days of MPT (r=0.68, r=0.71 respectively; P < 0.05).</p><p><b>CONCLUSIONS</b>Serum IL-13 levels and PBMC IL-13 mRNA expression in children with SRNS increase. MPT can inhibit the expression of protein and mRNA of IL-13 in these patients.</p>
Subject(s)
Adolescent , Child , Female , Humans , Male , Interleukin-13 , Blood , Genetics , Methylprednisolone , Nephrotic Syndrome , Blood , Drug Therapy , Proteinuria , Drug Therapy , RNA, MessengerABSTRACT
Objective To investigate the clinical feature,image of CT scan pulmonary,diagnosis and treatment response in children with pulmonary cavity,and discuss the method of diagnosis and the tactics of treatment for pulmonary cavity in children.Methods A retrospective study of 6 patients with pulmonary cavity,who were diagnosed and treated from Jul. 2003 to Oct. 2009 in Department of Pediatrics of the First Hospital Affiliated to China Medical University.The clinical manifestations,laboratory tests,image of CT scan pulmonary,microbiological evidence,diagnostic procedure and treatment response were collected and evaluated.Results Six patients all didn′t have history of lung di-sease,there were 4 boys and 2 girls,8-15 years old,average age was 10.5 years old.Two cases of them had unrelated pulmonary underlying diseases,1 case had hyperthyroidism,and the other had juvenile idiopathic arthritis and had complication of macrophage activation syndrome,the other 4 cases had no obvious history.All cases had fever (38-40 ℃),3 cases had cough and 1 case had chest pain.Staphylococcus aureus were cultured in 2 cases,no bacteria was cultured in other 4 cases;the count of white blood cell decreased in 2 cases and increased in 4 cases;C-reactive protein increased in 5 cases and was normal in 1 case;plasma IgE level increased in 2 cases and was normal in other 4 cases;plasma 1,3-beta-D-glucan of all 6 cases were negative.Pulmonary cavities were found in the first CT scan of the lungs in 5 cases and only 1 case of patient′s pulmonary cavities was found in the second CT scan of the lung.Five cases were diagnosed infective causes,1 case was diagnosed noninfectious cause,5 cases of infective causes had been treated with anti-microbial drugs for at least 1 week,1 case of noninfectious cause were treated with methylprednisolone cobined cyclosporin A for 2 weeks.Pulmonary CT scan was rechecked in all cases,and the state of the cases were improved before discharged from hospital.Conclusions The causes of pulmonary cavity in children are not only infective factors,but also some non-infective disease,especially some changes of image of pulmonary CT scan has diagnostic value,detailed past medical history and appropriate rechecking of chest radiographic check are very necessary for diagnosis,according to the result of microbial inspection and evaluation of treatment effect in time and then adjust the treatment protocols.
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Objective Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a multifunctional protein that has thc capacity to modify cellular activities and to modulate matrix turnover. This paper revealed the contributive role of TIMP-1 in progressive muscular dystrophy (PMD). Methods We examined the expression and cellular localization of TIMP-1 protein using biopsied frozen muscle from patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), congenital muscular dystrophy (CMD) by immunohistochemistry, double immunofluorescence and Western blot analysis. Results The results of immunohistochemistry and double immunofluorescence showed that TIMP-1 was positive only in vascular endothelial cells of normal muscles. Immunohistochemistry and Western blot analysis showed that the staining intensity was distinctly increased in some dystrophic muscles of PMD for TIMP-1. Double immunofluorescence revealed that TIMP-1 strongly expressed in the regenerating muscle fibers, macrophages and macrophage infiltrating necrotic fibers. Some activated fibroblasts in endomysium and perimysium of DMD and CMD muscles were also positive for TIMP1. Conclusion The functional consequence of overexpression of TIMP-1 in the dystrophic muscles is unknown, but the elevated local expression of TIMP-1 in diseased muscles of PMD and their distinct distribution pattern provide evidence that TIMP-1 may participate in the pathogenesis of PMD.
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Objective To explore the role of plasminogen activator inhibitor-1(PAI-1)in development of progressive fibrosis via the inhibition of extracellular matrix degradation,and to reveal the contributive role of PAI-1 in muscular dystrophy(MD).Methods Expression and cellular localization of PAI-1 protein were examined in frozen muscle specimens obtained via biopsy from 5 patients with duchenne muscular dystrophy(DMD),3 patients with becker muscular dystrophy(BMD),9 patients with congenital muscular dystrophy(CMD) and 4 cases with normal muscle by immunohistochemistry,double immunofluorescence and Western-blot analysis.Results PAI-1 was positive only in vascular endothelial cells of normal muscle.Both immunohistochemistry and Western-blot analysis showed that PAI-1 expression distinctly increased in most dystrophic muscles of MD than that in normal muscles.Double immunolabeling revealed that PAI-1 strongly expressed in cytoplasm and nuclei of regenerating muscle fibers,macrophages,macrophage infiltrating necrotic fibers.Some activated fibroblasts in endomysium and perimysium of DMD and CMD muscles were positive for PAI-1.Conclusions The functional consequence of overexpression of PAI-1 in dystrophic muscles is unknown but the elevated local expression of PAI-1 in diseased muscles of MD and their distinct distribution pattern provide evidence that PAI-1 participate in pathogenesis of MD.
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<p><b>OBJECTIVE</b>Progressive muscular dystrophy (PMD) is characterized by muscle fiber necrosis, regeneration, and endomysial fibrosis. Although absence of dystrophin and subsarcolemmic protein has been known as the cause of muscle fiber degeneration, pathogenesis of interstitial fibrosis is still unknown. The aim of this study was to investigate the role of connective tissue growth factor (CTGF) in PMD and its relationship with muscular fibrosis.</p><p><b>METHODS</b>Immunological localization of CTGF was examined in frozen muscle specimens obtained via biopsy from 8 patients with Duchenne muscular dystrophy (DMD), 2 patients with Becker muscular dystrophy (BMD), 6 patients with congenital muscular dystrophy (CMD) and 6 cases with normal muscle by immunohistochemistry, double immunofluorescence and Western blot analysis.</p><p><b>RESULTS</b>The results of immunohistochemistry and double immunofluorescence showed that CTGF was positive only in vessels of normal muscle. Both immunohistochemistry and Western blot analysis showed that CTGF expression was distinctly increased in dystrophy muscles of PMD than that in normal muscles. In dystrophy muscle, marked immunostaining of CTGF was not only observed in vascular walls, but also strongly expressed in the cytoplasm and nuclei of regenerating muscle fibers, and also immunolocalized in the muscle fiber sarcolemma of non-regenerating fibers. Double labeling with antibodies against CTGF and CD68 demonstrated that CTGF was expressed in some macrophages and some macrophage infiltrated necrotic fibers. CTGF was strongly expressed in endomysial and perimysial connective tissues of dystrophy muscles of patients with DMD, CMD and FCMD. Double immunolabeling revealed that most activated fibroblasts in perimysium and endomysium were positive for CTGF, but not all of connective tissues were co-localized with CTGF. Older cases with FCMD showed poor or no expression of CTGF in advanced fibrosis.</p><p><b>CONCLUSION</b>CTGF may play a role in the pathogenetic process of muscular dystrophy, and CTGF may be important for muscle repair and fibrosis.</p>