Background Pelizaeus-Merzbacher disease （PMD） is a rare X-linked recessive disorder with symptoms including nystagmus, impaired motor development, ataxia, and progressive spasticity. The proteolipidprotein 1 （PLP1...Background Pelizaeus-Merzbacher disease （PMD） is a rare X-linked recessive disorder with symptoms including nystagmus, impaired motor development, ataxia, and progressive spasticity. The proteolipidprotein 1 （PLP1） gene is the only pathogenic gene of PMD. Duplication of the PLP1 gene is the most frequent gene defect, accounting for 50%-70% of PMD cases, whereas point mutations in the coding sequence or the splice sites account for 10%-25% of PMD cases. This study aimed to identify PLP1 mutations in nine unrelated Chinese patients （P1-9） with PMD, and 14 subjects from the family of patient 2 were also described. Methods Genomic DNA was extracted from peripheral multiplex ligation-dependent probe amplification （MLPA）. AI amplified and analyzed using direct DNA sequencing. blood samples. Gene dosage was determined using the 7 exons and exon-intron boundaries of the PLP1 gene were Results Of these nine patients, there were four transitional, four classical, and one connatal PMD according to their clinical and radiological presentations. PLP1 duplications were identified in patients 1-7 with PMD. Their mothers were PLPI duplications carriers as well. Both duplication carriers and normal genotypes of PLP1 were identified in the family members of patient 2. A c.517C〉T （p. P173S） hemizygous missense mutation in exon 4 was found in patient 8 with PMD, and his mother was shown to be a heterozygote of this mutation. Conclusions We identified seven genomic duplications and one missense mutation （p. P173S） of the PLP1 gene in eight Chinese patients with PMD. This is the report about PLP1 mutations in PMD patients from the mainland of China.展开更多
To detect the function of proteolipid protein (PLP) peptide (residues 56-70) sp ecific CD 4 + T cells in experimental allergic encephalomyelitis (EAE) in Bioz zi AB/H mice (H 2A g7 ) Methods Biozzi AB/H mice were immu...To detect the function of proteolipid protein (PLP) peptide (residues 56-70) sp ecific CD 4 + T cells in experimental allergic encephalomyelitis (EAE) in Bioz zi AB/H mice (H 2A g7 ) Methods Biozzi AB/H mice were immunized by synthetic PLP 56 70 peptide (DYEYLINVIH AFQYV) which was emulsified by sonication with complete Freund’s adjuvant, a EAE model proven histologically and clinically Murine splenocytes and spinal cord infiltrated (SCI) T cells were stimulated by PLP 56 70 , then the CD 4 + T cells were isolated by Dynabeads, and confirmed by staining with anti CD 4 antibody Finally, the IL2 bioassay and IFN γ/IL4 ELISA were done to detect T cell proliferation and cytokine secretion after PLP 56 70 stimulation Results The histology of murine spinal cord showed a great number of lymphocytes infiltr ated the spinal cord; the clinical signs showed high scores (4 3) on the peak, as well as a good EAE model After being isolated by Dynabea ds , CD 4 + T cells showed high purification (>99%) by staining with anti CD 4 antibody IL2 bioassay showed that those T cells were PLP 56 70 specific T cells ELISA showed that those T cells had high IFN γ/IL4 ratio , indicating that they are T helper 1 (Th1) cells Conclusions PLP 56 70 specific splenocytes and SCI CD 4 + T cells in EAE from Bioz zi AB/H mice were detected and showed that both of them were P LP 56 70 specific Th1 cells It is beneficial to understand what kind o f role these T cells play in the development of展开更多
PCR amplification and sequencing of whole blood DNA from an individual with hereditary spastic paraplegia, as well as family members, revealed a fragment of proteolipid protein 1 （PLP1） gene exon 1, which excluded t...PCR amplification and sequencing of whole blood DNA from an individual with hereditary spastic paraplegia, as well as family members, revealed a fragment of proteolipid protein 1 （PLP1） gene exon 1, which excluded the possibility of isomer 1 expression for this family. The fragment sequence of exon 3 and exon 5 was consistent with the proteolipid protein 1 sequence at NCBI. In the proband samples, a PLP1 point mutation in exon 4 was detected at the basic group of position 844, T→C, phenylalanine→leucine. In proband samples from a male cousin, the basic group at position 844 was C, but gene sequencing signals revealed mixed signals of T and C, indicating possible mutation at this locus. Results demonstrated that changes in PLP1 exon 4 amino acids were associated with onset of hereditary spastic paraplegia.展开更多
In this study, we investigated the clinical relevance of anti-myelin antibodies in patients with neuromyelitis optica (NMO);titers of antibodies against myelin oligodendrocyte glycoproteins, proteolipid proteins and m...In this study, we investigated the clinical relevance of anti-myelin antibodies in patients with neuromyelitis optica (NMO);titers of antibodies against myelin oligodendrocyte glycoproteins, proteolipid proteins and myelin basic proteins were measured in the sera of patients with NMO and compared to healthy controls, as well as to patients with other diseases. The frequency of presence of anti-myelin antibodies in patients with NMO was significantly higher than that in healthy and diseased controls. The expanded disability status scale scores correlated with the titers of the anti-myelin antibodies. Patients with anti-myelin antibody exhibited other autoantibodies significantly more frequently than patients without the antibody. Anti-myelin antibodies may be useful markers for predicting severe clinical courses in patients with NMO.展开更多
The participation of immune mechanisms in the pathogenesis of dementia of Alzheimer type (AD) has been suggested. We examined T cell responses to myelin basic protein (MBP) and myelin prot...The participation of immune mechanisms in the pathogenesis of dementia of Alzheimer type (AD) has been suggested. We examined T cell responses to myelin basic protein (MBP) and myelin proteolipid protein (PLP) using an enzyme linked immunospot (ELISPOT) assay by enumerating mononuclear cells (MNC) that in blood and cerebrospinal fluid (CSF) secreted the cytokine interferon γ (IFN γ) spontaneously and after short time culture of the cells in presence of MBP or PLP. These myelin components are supposed to induce autoaggressive immunity in multiple sclerosis. MBP and PLP reactive IFN γ secreting cells were detected in patients with AD and, for comparison, in patients with other non inflammatory neurological diseases(OND) and patients with tension type headache (TH). Elevated levels of MBP and PLP reactive IFN γ secreting cells were found in blood in AD patients compared to OND and TH, such cells in AD patients were further enriched in CSF. Levels of MBP reactive as well as spontaneously IFN γ secreting cells in CSF were about 180 fold and 250 fold higher than in blood of AD patients, and also higher than the corresponding data in OND(30 fold and 20 fold) and in TH (120 fold and 20 fold). It is unclear whether the autoreactive T cell responses to MBP and PLP, especially accumulated in CSF, have any importance for the pathogenesis of AD.展开更多
Schizophrenia (SCZ) is a serious mental illness with unknown etiology, high recurrence rate and high disability rate, which has caused a great burden to individuals and society. There is no clear etiology and pathogen...Schizophrenia (SCZ) is a serious mental illness with unknown etiology, high recurrence rate and high disability rate, which has caused a great burden to individuals and society. There is no clear etiology and pathogenesis. Methylation of N6-methyladenosine (m6A) can regulate the nervous and mental system, and affect the function of the nervous system. Proteolipid protein 1 (PLP1) is a risk gene for schizophrenia. In this study we review the research progress on the pathogenesis of schizophrenia, m6A methylation, and PLP1 gene.展开更多
Schizophrenia(SCZ)is a serious mental illness whose etiology and pathogenesis are not yet clear.The level of miRNA may be a crucial factor in the occurrence and development of SCZ.This study found that miR-495 may reg...Schizophrenia(SCZ)is a serious mental illness whose etiology and pathogenesis are not yet clear.The level of miRNA may be a crucial factor in the occurrence and development of SCZ.This study found that miR-495 may regulate the susceptibility gene of SCZ and that proteolipid protein 1(PLP1)as a risk gene for schizophrenia may be involved in its pathogenesis.In this article we review the research progress related to hsa-miR-495-3p(miR-495),PLP1,and schizophrenia.展开更多
目的分析1个中国佩-梅病家系的临床特征及遗传学特点,以提高对该病的认识,并为国内佩-梅病患者的确诊、遗传咨询及产前诊断打下基础。方法收集临床诊断为佩-梅病的先证者及其家系成员的临床资料及14例 DNA 样本,对临床症状体征、影像学...目的分析1个中国佩-梅病家系的临床特征及遗传学特点,以提高对该病的认识,并为国内佩-梅病患者的确诊、遗传咨询及产前诊断打下基础。方法收集临床诊断为佩-梅病的先证者及其家系成员的临床资料及14例 DNA 样本,对临床症状体征、影像学特点进行分析,并采用多重连接依赖的探针扩增方法进行致病基因 PLP1重复突变检测,确定基因突变类型,分析基因型与表型的关系。结果先证者存在 PLP1基因重复突变,结合先证者及家系中其他男性患者临床特点可确诊为经典型佩-梅病。另检出3例家系中表型正常女性携带 PLP1基因重复突变。结论该家系由PLP1基因重复突变导致经典型佩-梅病,符合国外报道的基因型-表型关系;上述结果是为该家系提供可靠遗传咨询及产前诊断的依据;多重连接依赖的探针扩增这一新方法可用于快速、准确地检测PLP1的全基因重复。展开更多
文摘Background Pelizaeus-Merzbacher disease （PMD） is a rare X-linked recessive disorder with symptoms including nystagmus, impaired motor development, ataxia, and progressive spasticity. The proteolipidprotein 1 （PLP1） gene is the only pathogenic gene of PMD. Duplication of the PLP1 gene is the most frequent gene defect, accounting for 50%-70% of PMD cases, whereas point mutations in the coding sequence or the splice sites account for 10%-25% of PMD cases. This study aimed to identify PLP1 mutations in nine unrelated Chinese patients （P1-9） with PMD, and 14 subjects from the family of patient 2 were also described. Methods Genomic DNA was extracted from peripheral multiplex ligation-dependent probe amplification （MLPA）. AI amplified and analyzed using direct DNA sequencing. blood samples. Gene dosage was determined using the 7 exons and exon-intron boundaries of the PLP1 gene were Results Of these nine patients, there were four transitional, four classical, and one connatal PMD according to their clinical and radiological presentations. PLP1 duplications were identified in patients 1-7 with PMD. Their mothers were PLPI duplications carriers as well. Both duplication carriers and normal genotypes of PLP1 were identified in the family members of patient 2. A c.517C〉T （p. P173S） hemizygous missense mutation in exon 4 was found in patient 8 with PMD, and his mother was shown to be a heterozygote of this mutation. Conclusions We identified seven genomic duplications and one missense mutation （p. P173S） of the PLP1 gene in eight Chinese patients with PMD. This is the report about PLP1 mutations in PMD patients from the mainland of China.
文摘To detect the function of proteolipid protein (PLP) peptide (residues 56-70) sp ecific CD 4 + T cells in experimental allergic encephalomyelitis (EAE) in Bioz zi AB/H mice (H 2A g7 ) Methods Biozzi AB/H mice were immunized by synthetic PLP 56 70 peptide (DYEYLINVIH AFQYV) which was emulsified by sonication with complete Freund’s adjuvant, a EAE model proven histologically and clinically Murine splenocytes and spinal cord infiltrated (SCI) T cells were stimulated by PLP 56 70 , then the CD 4 + T cells were isolated by Dynabeads, and confirmed by staining with anti CD 4 antibody Finally, the IL2 bioassay and IFN γ/IL4 ELISA were done to detect T cell proliferation and cytokine secretion after PLP 56 70 stimulation Results The histology of murine spinal cord showed a great number of lymphocytes infiltr ated the spinal cord; the clinical signs showed high scores (4 3) on the peak, as well as a good EAE model After being isolated by Dynabea ds , CD 4 + T cells showed high purification (>99%) by staining with anti CD 4 antibody IL2 bioassay showed that those T cells were PLP 56 70 specific T cells ELISA showed that those T cells had high IFN γ/IL4 ratio , indicating that they are T helper 1 (Th1) cells Conclusions PLP 56 70 specific splenocytes and SCI CD 4 + T cells in EAE from Bioz zi AB/H mice were detected and showed that both of them were P LP 56 70 specific Th1 cells It is beneficial to understand what kind o f role these T cells play in the development of
文摘PCR amplification and sequencing of whole blood DNA from an individual with hereditary spastic paraplegia, as well as family members, revealed a fragment of proteolipid protein 1 （PLP1） gene exon 1, which excluded the possibility of isomer 1 expression for this family. The fragment sequence of exon 3 and exon 5 was consistent with the proteolipid protein 1 sequence at NCBI. In the proband samples, a PLP1 point mutation in exon 4 was detected at the basic group of position 844, T→C, phenylalanine→leucine. In proband samples from a male cousin, the basic group at position 844 was C, but gene sequencing signals revealed mixed signals of T and C, indicating possible mutation at this locus. Results demonstrated that changes in PLP1 exon 4 amino acids were associated with onset of hereditary spastic paraplegia.
文摘In this study, we investigated the clinical relevance of anti-myelin antibodies in patients with neuromyelitis optica (NMO);titers of antibodies against myelin oligodendrocyte glycoproteins, proteolipid proteins and myelin basic proteins were measured in the sera of patients with NMO and compared to healthy controls, as well as to patients with other diseases. The frequency of presence of anti-myelin antibodies in patients with NMO was significantly higher than that in healthy and diseased controls. The expanded disability status scale scores correlated with the titers of the anti-myelin antibodies. Patients with anti-myelin antibody exhibited other autoantibodies significantly more frequently than patients without the antibody. Anti-myelin antibodies may be useful markers for predicting severe clinical courses in patients with NMO.
文摘The participation of immune mechanisms in the pathogenesis of dementia of Alzheimer type (AD) has been suggested. We examined T cell responses to myelin basic protein (MBP) and myelin proteolipid protein (PLP) using an enzyme linked immunospot (ELISPOT) assay by enumerating mononuclear cells (MNC) that in blood and cerebrospinal fluid (CSF) secreted the cytokine interferon γ (IFN γ) spontaneously and after short time culture of the cells in presence of MBP or PLP. These myelin components are supposed to induce autoaggressive immunity in multiple sclerosis. MBP and PLP reactive IFN γ secreting cells were detected in patients with AD and, for comparison, in patients with other non inflammatory neurological diseases(OND) and patients with tension type headache (TH). Elevated levels of MBP and PLP reactive IFN γ secreting cells were found in blood in AD patients compared to OND and TH, such cells in AD patients were further enriched in CSF. Levels of MBP reactive as well as spontaneously IFN γ secreting cells in CSF were about 180 fold and 250 fold higher than in blood of AD patients, and also higher than the corresponding data in OND(30 fold and 20 fold) and in TH (120 fold and 20 fold). It is unclear whether the autoreactive T cell responses to MBP and PLP, especially accumulated in CSF, have any importance for the pathogenesis of AD.
基金Yunnan Provincial Department of Science and Technology Project(202101AY070001-224).
文摘Schizophrenia (SCZ) is a serious mental illness with unknown etiology, high recurrence rate and high disability rate, which has caused a great burden to individuals and society. There is no clear etiology and pathogenesis. Methylation of N6-methyladenosine (m6A) can regulate the nervous and mental system, and affect the function of the nervous system. Proteolipid protein 1 (PLP1) is a risk gene for schizophrenia. In this study we review the research progress on the pathogenesis of schizophrenia, m6A methylation, and PLP1 gene.
基金Yunnan Provincial Department of Science and Technology Project(202101AY070001-224).
文摘Schizophrenia(SCZ)is a serious mental illness whose etiology and pathogenesis are not yet clear.The level of miRNA may be a crucial factor in the occurrence and development of SCZ.This study found that miR-495 may regulate the susceptibility gene of SCZ and that proteolipid protein 1(PLP1)as a risk gene for schizophrenia may be involved in its pathogenesis.In this article we review the research progress related to hsa-miR-495-3p(miR-495),PLP1,and schizophrenia.
