Overexpression of methyl-CpG-binding protein 2 and autoimmunity: evidence from MECP2 duplication syndrome, lupus, MECP2 transgenic and Mecp2 deficient mice

Sawalha, Amr H.

doi:10.1177/0961203313497119

Cited by 11 publications

(5 citation statements)

References 25 publications

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“…However, Yang and colleagues identified immune defects among the patients with MECP2 DS had no association with IRAK1 duplication by transgenic mice that overexpressed MECP2 without IRAK1 duplication [ 21 ]. This conclusion was supported by Sawalha [ 22 ]. Chronic intestinal pseudo–obstruction (CIPO), thrombcytopaenia, patent ductus arteriosus (PDA), malrotation were found in two families with the duplications involved only the FLNA gene [ 23 ].…”

Section: Discussionsupporting

confidence: 67%

MECP2 duplication syndrome in a Chinese family

et al. 2015

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BackgroundMethyl-CpG-binding protein 2 (MeCP2) is a key transcriptional regulator of gene expression in the maintenance and development of the central nervous system. Loss- or gain-function of this gene may contribute to neurodevelopmental disorders. The aim of this study is to delineate the clinical characteristics of MECP2 duplication syndrome and the hereditary mechanism in a Chinese family.Case presentationWe identified a Chinese family with three persons carry MECP2 gene duplication: a boy, his mother and his grandmother. The duplication segment which was detected by multiplex ligation-dependent probe amplification (MLPA) included gene MECP2, interleukin-1 receptor-associated kinase 1 (IRAK1), filamin A (FLNA), and L1 cell adhesion molecule (L1CAM). Furthermore, array comparative genomic hybridization (aCGH) was performed on the mother, showed that MECP2 containing duplication was 510 Kb (153,113,885-153,624,154), including 16 other genes except MECP2. The boy showed most symptoms of MECP2 duplication syndrome. His mother and maternal grandmother were asymptomatic. Both female carriers had a skewed X chromosome inactivation (XCI), which were 80:20 and 74:26 respectively.ConclusionTo our knowledge, this is the second reported Chinese Han family with MECP2-containing duplications. And this patient had recurrent respiratory infections which was different from the first two Chinese-brother cases. MECP2 is the core gene responsible for MECP2 duplication syndrome. XCI may play an important role in modulating the clinical manifestation.

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Section: Discussionsupporting

confidence: 67%

MECP2 duplication syndrome in a Chinese family

et al. 2015

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“…Also, two proteins have been involved in regulating the immune response. Recent studies found that MeCP2 is important for the expression of sustained Foxp3 in Tregs during inflammation and was indispensable for the differentiation of naïve CD4 + T cells into Th1 and Th17 cells and for Th1 or Th17-mediated pathologies in vitro and in vivo ( 50 , 51 ). Furthermore, MeCP2 protein undergoes multiple SUMOylation and acetylation, which impact its functions ( 52 ).…”

Section: Discussionmentioning

confidence: 99%

Comparative Analysis of Global Proteome and Lysine Acetylome Between Naive CD4+ T Cells and CD4+ T Follicular Helper Cells

et al. 2021

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As a subgroup of CD4+ T helper cells, follicular helper T (Tfh) cells provide help to germinal center B cells and mediate the development of long-lived humoral immunity. Dysregulation of Tfh cells is associated with several major autoimmune diseases. Although recent studies showed that Tfh cell differentiation is controlled by the transcription factor Bcl6, cytokines, and cell-cell signals, limited information is available on the proteome and post-translational modifications (PTMs) of proteins in human Tfh cells. In the present study, we investigated quantitative proteome and acetylome in human naive CD4+ T cells and in vitro induced Tfh (iTfh) cells using the tandem mass tag (TMT) labeling technique, antibody-based affinity enrichment, and high-resolution liquid chromatography-mass spectrometry (LC-MS)/mass spectrometry (MS) analysis. In total, we identified 802 upregulated proteins and 598 downregulated proteins at the threshold of 1.5-fold in iTfh cells compared to naive CD4+ T cells. With the aid of intensive bioinformatics, the biological process, the cellular compartment, the molecular function, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein–protein interaction of these differentially expressed proteins were revealed. Moreover, the acetylome data showed that 22 lysine (K) acetylated proteins are upregulated and 26 K acetylated proteins are downregulated in iTfh cells compared to the naive CD4+ T cells, among which 11 differentially acetylated K residues in core histones were identified, indicating that protein acetylation and epigenetic mechanism are involved in regulating Tfh cell differentiation. The study provides some important clues for investigating T cell activation and Tfh cell differentiation.

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“…Moreover, cases with a duplicated region inclusive of IRAK1 with no history of respiratory infections have been reported [ 42 , 53 , 55 ], as has a female patient who had recurrent respiratory infections but not a duplicated IRAK1 region [ 43 ]. Mice models of MDS with an overexpression of human MECP2 without IRAK1 have also been shown to be immunodeficient suggesting that immune defects in MDS may likely be independent of IRAK1 duplication [ 126 , 127 ].…”

Section: The Syndromic Phenotype Of Mecp2 Duplicat...mentioning

confidence: 99%

A brief history of MECP2 duplication syndrome: 20-years of clinical understanding

Downs

Baynam

et al. 2022

Orphanet J Rare Dis

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MECP2 duplication syndrome (MDS) is a rare, X-linked, neurodevelopmental disorder caused by a duplication of the methyl-CpG-binding protein 2 (MECP2) gene—a gene in which loss-of-function mutations lead to Rett syndrome (RTT). MDS has an estimated live birth prevalence in males of 1/150,000. The key features of MDS include intellectual disability, developmental delay, hypotonia, seizures, recurrent respiratory infections, gastrointestinal problems, behavioural features of autism and dysmorphic features—although these comorbidities are not yet understood with sufficient granularity. This review has covered the past two decades of MDS case studies and series since the discovery of the disorder in 1999. After comprehensively reviewing the reported characteristics, this review has identified areas of limited knowledge that we recommend may be addressed by better phenotyping this disorder through an international data collection. This endeavour would also serve to delineate the clinical overlap between MDS and RTT.

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Overexpression of methyl-CpG-binding protein 2 and autoimmunity: evidence from MECP2 duplication syndrome, lupus, MECP2 transgenic and Mecp2 deficient mice

Cited by 11 publications

References 25 publications

MECP2 duplication syndrome in a Chinese family

MECP2 duplication syndrome in a Chinese family

Comparative Analysis of Global Proteome and Lysine Acetylome Between Naive CD4+ T Cells and CD4+ T Follicular Helper Cells

A brief history of MECP2 duplication syndrome: 20-years of clinical understanding

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