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...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.展开更多
DNA methyltransferase(MTase)activity detection has received increasing attention as a promising biomarker and therapeutic target.However,most of these detection methods rely on endonuclease digestion and signal groups...DNA methyltransferase(MTase)activity detection has received increasing attention as a promising biomarker and therapeutic target.However,most of these detection methods rely on endonuclease digestion and signal groups labeling.Herein,we present a novel platform for sensing DNA MTase activity that overcomes these limitations.Our approach is both endonuclease-free and label-free,utilizing a combination of a high-affinity streptavidin-methyl-CpG-binding domain(SA-MBD)protein and surface plasmon resonance(SPR)technology.The SA-MBD protein specifically recognizes a hairpin probe containing methylated CpG sites,which is treated with M.SssI MTase.This recognition event generates a corresponding SPR response signal.The limit of detection is as low as 0.016 U/mL,owing to the high-affinity of the SA-MBD protein.Notably,we have demonstrated the feasibility of our method for M.SssI MTase activity analysis in serum and inhibitor screening,which implies the potential prospects for biomedical research.展开更多
BACKGROUND Rett syndrome is a monogenic X-linked dominant condition that affects 1/(10000-15000)girls due to de novo mutations in the methyl-CpG binding protein 2(MECP2)gene mapped to chromosome Xq28.The disease-causi...BACKGROUND Rett syndrome is a monogenic X-linked dominant condition that affects 1/(10000-15000)girls due to de novo mutations in the methyl-CpG binding protein 2(MECP2)gene mapped to chromosome Xq28.The disease-causing gene was identified as a mutation in the MECP2 gene,which is found in approximately 80%of patients diagnosed with Rett syndrome.Although chromosomal changes resulting in del(15)(q11q13)are usually associated with Angelman and Prader-Willi syndrome,very few cases,if any,of Rett syndrome with terminal 15q22-qter deletion have been published in English literature.CASE SUMMARY In this study,we report an unusual and rare clinical presentation of Rett syndrome in a 12-year-old Sudanese girl.The patient was brought in by her parents,complaining of gradual onset of abnormal walking,abnormal hand movement,loss of speech,and mental retardation for ten years.There was no reported history of convulsions or loss of consciousness.Clinical examination revealed microcephaly with no other apparent dysmorphic features,intact cranial nerves,and abnormal gait.She showed repetitive and stereotyped behaviors,including hand flapping,stimming,and chest pounding,which were concomitant with autism spectrum disorder.Magnetic resonance imaging and electroencephalography investigations were normal,and cytogenetic analysis showed 46,XX,del(15)(q22qter).Further molecular analysis using whole sequencing of MECP2 revealed an alteration cytosine>thymine at nucleotide 401,leading to phenylalanine replacing a serine at amino acid position 134.CONCLUSION This case,the first reported instance of Rett syndrome in Sudan,is of significant interest.The patient carries both the MECP2 gene mutation and the chromosome 15q22-qter deletion,which may explain the autistic behavior with atypical presentation of Rett syndrome.This report expands the genetic diversity of Rett syndrome,demonstrating how co-occurring 15q22-qter deletions can reshape MECP2-associated phenotypes in Rett syndrome.展开更多
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 depri...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.展开更多
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 pat...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.展开更多
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 maintenan...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.展开更多
文摘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.
基金funded by the National Natural Science Foundation of China(61901527,82300051)National Key Research and Development Program of China(2022YFF0710803,2022YFF0710800)Fundamental Research Funds for the Central Universities(2632021ZD02).
文摘DNA methyltransferase(MTase)activity detection has received increasing attention as a promising biomarker and therapeutic target.However,most of these detection methods rely on endonuclease digestion and signal groups labeling.Herein,we present a novel platform for sensing DNA MTase activity that overcomes these limitations.Our approach is both endonuclease-free and label-free,utilizing a combination of a high-affinity streptavidin-methyl-CpG-binding domain(SA-MBD)protein and surface plasmon resonance(SPR)technology.The SA-MBD protein specifically recognizes a hairpin probe containing methylated CpG sites,which is treated with M.SssI MTase.This recognition event generates a corresponding SPR response signal.The limit of detection is as low as 0.016 U/mL,owing to the high-affinity of the SA-MBD protein.Notably,we have demonstrated the feasibility of our method for M.SssI MTase activity analysis in serum and inhibitor screening,which implies the potential prospects for biomedical research.
文摘BACKGROUND Rett syndrome is a monogenic X-linked dominant condition that affects 1/(10000-15000)girls due to de novo mutations in the methyl-CpG binding protein 2(MECP2)gene mapped to chromosome Xq28.The disease-causing gene was identified as a mutation in the MECP2 gene,which is found in approximately 80%of patients diagnosed with Rett syndrome.Although chromosomal changes resulting in del(15)(q11q13)are usually associated with Angelman and Prader-Willi syndrome,very few cases,if any,of Rett syndrome with terminal 15q22-qter deletion have been published in English literature.CASE SUMMARY In this study,we report an unusual and rare clinical presentation of Rett syndrome in a 12-year-old Sudanese girl.The patient was brought in by her parents,complaining of gradual onset of abnormal walking,abnormal hand movement,loss of speech,and mental retardation for ten years.There was no reported history of convulsions or loss of consciousness.Clinical examination revealed microcephaly with no other apparent dysmorphic features,intact cranial nerves,and abnormal gait.She showed repetitive and stereotyped behaviors,including hand flapping,stimming,and chest pounding,which were concomitant with autism spectrum disorder.Magnetic resonance imaging and electroencephalography investigations were normal,and cytogenetic analysis showed 46,XX,del(15)(q22qter).Further molecular analysis using whole sequencing of MECP2 revealed an alteration cytosine>thymine at nucleotide 401,leading to phenylalanine replacing a serine at amino acid position 134.CONCLUSION This case,the first reported instance of Rett syndrome in Sudan,is of significant interest.The patient carries both the MECP2 gene mutation and the chromosome 15q22-qter deletion,which may explain the autistic behavior with atypical presentation of Rett syndrome.This report expands the genetic diversity of Rett syndrome,demonstrating how co-occurring 15q22-qter deletions can reshape MECP2-associated phenotypes in Rett syndrome.
基金supported by grants from Universidad de Guadalajara(PROSNI 2016,2017-8)to REGCpartially by grants from Consejo Nacional de Ciencia y Tecnologia(CONACyT No.PN 2016-01-465 and INFR-280414)+1 种基金PRODEP(213544)to OGPthe CONACyT Fellowship grant(374823)to AHG
文摘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.
基金sponsored by the Ph.D.Independent Research Projects of Wuhan University,No.201130302020017a grant from the Science and Technology Bureau of Hubei Province,No.2011CDB511the National Natural Science Foundation of China,No.81170769
文摘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.
基金We want to thank the support from NIH-NINDS F31NS084551 NRSA predoctoral fellowship and the Jérôme LeJeune Foundation.
文摘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.
