ABSTRACT
<p><b>OBJECTIVE</b>To investigate the association between genotype and phenotype of microdeletion and microduplication syndromes (MMSs) and the pathogenesis of pathogenic copy number variations (CNVs).</p><p><b>METHODS</b>A total of 50 children with MMSs diagnosed by chromosomal microarray analysis (CMA) from June 2013 to September 2015 were enrolled, and the clinical manifestations and features of pathogenic CNVs were analyzed.</p><p><b>RESULTS</b>The main clinical manifestations of children with MMSs included mental retardation, developmental delay, short stature, and unusual facies, with the presence of abnormalities in multiple systems. There were 54 pathogenic CNVs in total, consisting of 36 microdeletion segments and 18 microduplication segments, with sizes ranging from 28 kb to 48.5 Mb (mean 13.86 Mb). Pathogenic CNVs often occurred in chromosomes X, 15, and 1.</p><p><b>CONCLUSIONS</b>The clinical manifestations of MMSs are not specific, and a genotype-first approach can be used for diagnosis. Mode of inheritance, type of recombination (deletion or duplication), size of segment, and functional genes included helps with the interpretation of CNVs of de novo mutations, and in-depth research on rare pathogenesis may become breakthrough points for the identification of new MMSs.</p>
Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Chromosome Deletion , Chromosome Duplication , DNA Copy Number Variations , Developmental Disabilities , Genetics , Intellectual Disability , Genetics , Phenotype , Retrospective Studies , SyndromeABSTRACT
Objective To explore the therapeutic effect of intravenous immunoglobulin(IVIG)on children with epilepsy and its mechanism to provide evidence for clinical application of IVIG into the management of children with epilepsy.Methods We retrospectively reviewed the data of 98 children with childhood-onset epilepsy treated with IVIG.Sixty-six health children were chosen as control group.The efficacy,tolerability,safety and serum immunological parameters of these patients were mainly evaluated and the serum immunologicla parameters,including T-1ymphocyte subsets and serum immunoglobulin,were detected by flow cytometry and immunoturbidimetry,respectively.Results The total effective rotes were 78.57%.Partial seizures-free rate(77.27%)and generalized seizures-free rate(79.63%)were not statistically different(P>0.05).The effective rate of symptomatic epilepsy (88.23%)and that of idiopathic epilepsy(68.09%)were significantly different(P<0.05).No significant difference of effective rates was found among the patients with new onset epilepsy having IVIG as first-line treatment(89.29%),the patients with monotherapy of MG after withdrawing AEDs(69.23%)and the patients with IVIG adjunct to other AEDs(75.43%,P>0.05).Thirty-one out of 45 patients with abnormal MRI on the brain showed improvement 6 months after treatment with IVIG.Thirteen patients had drug reactions,but could be tolerable for all these patients.Compared with the control group,epileptic groups showed significantly increased expressions of CD19~+B and CD20~+B cells and significantly decreased CD3~+CD4~+T cells.After the treatment with IVIG,epileptic groups showed significantly decreased expressions of CD19~+B and CD20~+B cells and significantly increased CD3~+CD4~+T cells as compared with the epileptic groups before the treatment.Three weeks and six months after the IVIG treatments,the level of serum IgG in the epileptic groups was significantly elevated as compared with that before treatment.Conclusion IVIG treatment,decreasing the expressions of CD19~+B and CD20~+B,is effective in treating patients with symptomatic epilepsy following immune disorders.