Methyl-CpG-Binding protein 2 duplication syndrome in a Chinese patient:A case report and review of the literature

BACKGROUND Chromosomal Xq28 region duplication encompassing methyl-CpG-binding protein 2(MECP2)results in an identifiable phenotype and global developmental delay known as MECP2 duplication syndrome(MDS).This syndrome has a wide range of clinical manifestations,including abnormalities in appearance,neurodevelopment,and gastrointestinal motility;recurrent infections;and spasticity.Here,we report a case of confirmed MDS at our institution.CASE SUMMARY A 12-year-old Chinese boy presented with intellectual disability(poor intellectual[reasoning,judgment,abstract thinking,and learning]and adaptive[lack of communication and absent social skills,apraxia,and ataxia]functioning)and dysmorphism.He had no history of recurrent infections,seizures,or bowel dysfunction,which is different from that in reported cases.Microarray comparative genomic hybridization confirmed MECP2 duplication in the patient and his mother who is a carrier.The duplication size was the same in the patient and his mother.No prophylactic antibiotic or anti-seizure therapy was offered to the patient or his mother before or after the consultation.CONCLUSION MDS is rare and has various clinical presentations.Clinical suspicion is critical in patients presenting with developmental delays.

Melatonin modifies SOX2^+ cell proliferation in dentate gyrus and modulates SIRT1 and MECP2 in long-term sleep deprivation

Melatonin is a pleiotropic molecule that,after a short-term sleep deprivation,promotes the proliferation of neural stem cells in the adult hippocampus.However,this effect has not been observed in long-term sleep deprivation.The precise mechanism exerted by melatonin on the modulation of neural stem cells is not entirely elucidated,but evidence indicates that epigenetic regulators may be involved in this process.In this study,we investigated the effect of melatonin treatment during a 96-hour sleep deprivation and analyzed the expression of epigenetic modulators predicted by computational text mining and keyword clusterization.Our results showed that the administration of melatonin under sleep-deprived conditions increased the MECP2 expression and reduced the SIRT1 expression in the dentate gyrus.We observed that let-7 b,mir-132,and mir-124 were highly expressed in the dentate gyrus after melatonin administration,but they were not modified by sleep deprivation.In addition,we found more Sox2^+/5-bromo-2’-deoxyuridine(BrdU)^+cells in the subgranular zone of the sleep-deprived group treated with melatonin than in the untreated group.These findings may support the notion that melatonin modifies the expression of epigenetic mediators that,in turn,regulate the proliferation of neural progenitor cells in the adult dentate gyrus under long-term sleep-deprived conditions.All procedures performed in this study were approved by the Animal Ethics Committee of the University of Guadalajara,Mexico(approval No.CI-16610)on January 2,2016.

Is X-linked methyl-CpG binding protein 2 a new target for the treatment of Parkinson's disease?

X-linked methyl-CpG binding protein 2 mutations can induce symptoms similar to those of Parkinson’s disease and dopamine metabolism disorders, but the specific role of X-linked methyl-CpG binding protein 2 in the pathogenesis of Parkinson’s disease remains unknown. In the present study, we used 6-hydroxydopamine-induced human neuroblastoma cell （SH-SY5Y cells） injury as a cell model of Parkinson’s disease. The 6-hydroxydopamine （50 μmol/L） treatment decreased protein levels for both X-linked methyl-CpG binding protein 2 and tyrosine hydroxylase in these cells, and led to cell death. However, overexpression of X-linked methyl-CpG binding protein 2 was able to ameliorate the effects of 6-hydroxydopamine, it reduced 6-hydroxydopamine-induced apoptosis, and increased the levels of tyrosine hydroxylase in SH-SY5Y cells. These findings suggesting that X-linked methyl-CpG binding protein 2 may be a potential therapeutic target for the treatment of Parkinson’s disease.

Regulatory functions and pathological relevance of the MECP23′UTR in the central nervous system

Methyl-CpG-binding protein 2(MeCP2),encoded by the gene MECP2,is a transcriptional regulator and chromatinremodeling protein,which is ubiquitously expressed and plays an essential role in the development and maintenance of the central nervous system(CNS).Highly enriched in post-migratory neurons,MeCP2 is needed for neuronal maturation,including dendritic arborization and the development of synapses.Loss-of-function mutations in MECP2 cause Rett syndrome(RTT),a debilitating neurodevelopmental disorder characterized by a phase of normal development,followed by the progressive loss of milestones and cognitive disability.While a great deal has been discovered about the structure,function,and regulation of MeCP2 in the time since its discovery as the genetic cause of RTT,including its involvement in a number of RTT-related syndromes that have come to be known as MeCP2-spectrum disorders,much about this multifunctional protein remains enigmatic.One unequivocal fact that has become apparent is the importance of maintaining MeCP2 protein levels within a narrow range,the limits of which may depend upon the cell type and developmental time point.As such,MeCP2 is amenable to complex,multifactorial regulation.Here,we summarize the role of the MECP23'untranslated region(UTR)in the regulation of MeCP2 protein levels and how mutations in this region contribute to autism and other non-RTT neuropsychiatric disorders.