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OBJECTIVE@#To explore the molecular basis for a child featuring with Floating-Harbor syndrome.@*METHODS@#The 2-year-and-8-month-old child presented with retarded growth and language development. Genomic DNA was extracted from peripheral blood samples from the child and his parents with informed consent and subjected to whole exome sequencing. Suspected variants were verified by Sanger sequencing. Pathogenecity of the variants were predicted by using bioinformatic tools.@*RESULTS@#The child was found to carry a de novo frameshift variant c.7273dupA (p. Thr2425Asnfs*18) in the SRCAP gene. The variant was unreported previously and predicted to be pathogenic by MutationTaster. Analysis using HomoloGene system and MEGA software indicated position 2425 of the SRCAP protein to be highly conserved. Substitution of amino acid (Thr) at this position may cause destruction of three AT-hook domains (Amino acid 2857-2869, 2936-2948 and 3004-3016) and serious damage to the function of SRCAP protein.@*CONCLUSION@#The patient's condition may be attributed to the de novo frameshift variant c.7273dupA (p. Thr2425Asnfs*18) of the SRCAP gene. Above finding can facilitate diagnosis of Floating-Harbor syndrome among Chinese population.
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Objective To summarize the clinical manifestations, diagnosis, and treatment of infantile Sandhoff disease. Methods The clinical data of one case with infantile Sandhoff disease were reviewed retrospectively. The related literatures were reviewed. Results The girl aged 1 year and 2 months suffered from psychomotor regression and intractable convulsions. The parents were consanguineous marriage. The fundus microscopy showed fundus erythema. Brain magnetic resonance imaging showed an abnormal signal of long T2WI and identical T1WI at left pons, white matter edema, and diffuse demyelination. No abnormal karyotype was observed. A chromosome microarray suggested multiple large homozygous chromosomes segments. The second generation gene sequencing showed deletion of c.1263_1268delTGAAGT:P. (Glu422_Val423del) deletion in exon 11 and a shear mutation of c.1614_2A>G:P? in intron 13 of HEXB gene which were carried by her parents respectively . The activity of HexA, HexA & HexB were 84 and 112 nmol?mg?1?h?1, respectively. Finally, this girl was diagnosed of infantile Sandhoff's disease. After treatment with valproate, levetiracetam combined with antiepileptic and glucocorticoids, episodes of convulsions were decreased gradually, and the reaction was better than before. In 5 months of follow up, the condition was stable, and no progression and no seizures exist. Her mother got pregnant again and received an amniocentesis on her 21+6 weeks of pregnancy, and results suggest that the fetus had the same mutation as this girl. Conclusions Sandhoff's disease is a type of rare hereditary lysosomal disease, characterized by progressive neurological impairment. Currently there are no effective treatments. Genetic testing is helpful in the diagnosis and prenatal diagnosis.
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Objective To explore the effect of bone marrow mesenchymal stem cells (MSCs) on LPS-stimulated BV2 microglia in inflammatory reaction. Methods Mouse MSCs were isolated and purified by adherence screening. The routinely cultured BV2 microglia in vitro were divided into PBS control group (group A),PBS plus MSCs treatment group(group B),LPS stimulation group(group C) and LPS plus MSCs group(group D).MSCs and BV2 microglia were cultured in the transwell co-culture system for 24 hours. We observed BV2 microglia morphological changes under the microscope,detected the concentrations of NO by Griess reaction,and the level of IL-1β,TNF-αby ELISA. Results MSCs can improve the morphology of activated microglia. The concentrations of TNF-a, IL-1βand N0 in culture supernatants were increased significantly (P < 0.05) after microglia activation, however, at the present of MSCs,the concentration of these inflammatory factors declined dramaticly (P<0.05). Conclusions MSCs can significantly inhibit the activation of microglia. It may play a neuroprotective effect by reducing the inflammation of microglia. MSCs showing anti-inflammatory effects through non-direct contact with nicroglial, suggesting that MSCs outside the brain may also inhibit the activation of microglia.