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Genetics
Published in Stephan Strobel, Lewis Spitz, Stephen D. Marks, Great Ormond Street Handbook of Paediatrics, 2019
Jane A. Hurst, Richard H. Scott
Classical Rett syndrome affects females. There is apparent normal early development followed by a period of developmental regression in terms of language and motor skills at between 6 and 18 months of age. Subsequently, speech is typically absent and development remains severely delayed in all areas (Fig. 15.24). Stereotypic midline hand movements are common, replacing purposeful hand movements. Head growth decelerates. Occasionally males are observed with MECP2 mutations. They manifest with a severe neonatal encephalopathy. Diagnosis: mutation analysis of the MECP2 gene.Inheritance: X-linked dominant with almost all mutations occurring de novo.Differential diagnosis: see Table 12; metabolic disorders.
Animal Models of Down Syndrome and Other Genetic Diseases Associated with Mental Retardation
Published in Merlin G. Butler, F. John Meaney, Genetics of Developmental Disabilities, 2019
Angela J. Villar, Charles J. Epstein
Classic Rett syndrome (RTT) is a neurodevelopmental disorder found almost solely in females, with prevalence of 1:10,000–20,000 (164). The classic RTT patient shows apparently normal development for 6–18 months but then fails to acquire new skills and enters a period of regression in which motor and language skills are lost (164). Clinical characteristics of the syndrome include abnormal motor gait, stereotypic hand wringing movements, and autistic-like behavior. Affected girls also exhibit speech abnormalities and severe cognitive deficits in most cases (165). In addition to classic RTT, there is an extraordinary range of phenotypes in females as a result of differences in X-chromosome inactivation (XCI) patterns and in the specific mutations that are present in the disease-causing gene, MECP2 (166). This gene encodes the methyl-CpG binding protein 2 (MeCP2) which is thought to be a general transcriptional repressor. In males, different MECP2 mutations can produce phenotypes ranging from a severe neonatal encephalopathy and infantile death to early-onset psychosis (167).
Inorganic Chemical Pollutants
Published in William J. Rea, Kalpana D. Patel, Reversibility of Chronic Disease and Hypersensitivity, Volume 4, 2017
William J. Rea, Kalpana D. Patel
Altered BDF transcripts have been reported in Rett syndrome patients, a neurodevelopmental disorder characterized by mutations of MeCP2,407,408 and BDNF levels are decreased in the brain of MeCP2 mutant mice.409,410 Other studies have shown that reduced phosphorylation of MeCP2 at S421 reduces dendritic branching and alters the morphology of dendritic spines,384 effects that have also been observed in the Pb2+-exposed brain.411,422 They should note that the phosphorylation of MeCP2 at S421 is selective for CaMKII and no other kinases,384 and they have previously shown that CaMKII activity and protein levels are significantly reduced in the hippocampus of rats exposed to Pb2+ during development.372 Because MeCP2 is a master regulator of transcription, the present findings suggest that the transcriptional activity of other genes whose promoters are regulated by MeCP2 may also be affected by Pb2+ exposure.
Association between MeCP2 and Smad7 in the pathogenesis and development of pathological scars
Published in Journal of Plastic Surgery and Hand Surgery, 2021
Dan Li, E. Yang, Juan Zhao, Hengshu Zhang
Methyl-CpG binding protein family inhibits gene expression by combining with hypermethylated promoters, and is involved in the subsequent effects of DNA methylation [7]. As an important member of the methyl-CpG binding protein family, methylated binding protein 2 (MeCP2) is widely considered to be a transcription repressor that silences methylated genes. Under the synergy of histone deacetylase (HDAC), MeCP2 inhibits gene transcription by combining with a hypermethylated gene promoter [8]. Relevant studies have shown that the expression of MeCP2 is increased in the fibroblasts derived from fibrotic tissues [9]. After inhibiting MeCP2 expression, the expression of fibrosis-related inflammatory cytokines is decreased, and the degree of tissue fibrosis is also significantly reduced [10]. In addition, the effect of TGF-β on fibrosis induction is weakened after MeCP2 gene silencing [11].
MeCP2 attenuates cardiomyocyte hypoxia/reperfusion-induced injury via regulation of the SFRP4/Wnt/β-catenin axis
Published in Biomarkers, 2021
Nan Li, Tao Zhang, Mengying He, Yudong Mu
Methylated CpG binding protein 2 (MeCP2) is a member of the methyl-CpG-binding domain (MBD) family (Fasolino and Zhou 2017, Johnson et al. 2017). As an important transcription inhibitor, the domain contained in MeCP2 has the ability to regulate chromosome conformation, regulate transcriptional activation and participate in RNA splicing (Lagger et al. 2017, Mellios et al. 2018, Lee et al. 2020). It plays an important role in DNA damage repair, cell apoptosis, cell proliferation, cell cycle regulation, cell differentiation, stress, the maintenance of genome stability, and the post-transcriptional modification of genes (Meng et al. 2014, Filosa et al. 2015, Fasolino and Zhou 2017, Lin et al. 2020). Growing evidence shows that MeCP2 is widely involved in the occurrence and development of various human diseases (Meng et al. 2014, Signorini et al. 2016, Zhang et al. 2020a). Recently, a report indicated that MeCP2 has decreased expression in human cardiovascular diseases and further data proved that it can be used as a prognostic marker of heart failure (Wang et al. 2018), but its functional mechanism in I/R injury is still unclear. The present study aimed to investigate the role and underlying mechanism of MeCP2 in I/R injury, and suggested that the utilisation of MeCP2 as a potential molecular therapeutic target of I/R treatment.
Medical Issues in Adults with Rett Syndrome – A National Survey
Published in Developmental Neurorehabilitation, 2020
Mari Wold Henriksen, Hilde Breck, Stephen von Tetzchner, Benedicte Paus, Ola H. Skjeldal
All participants without a known mutation were offered genetic analyses (one participant was not tested). Participants with negative results on earlier tests were retested with an exome-based high throughput sequencing (HTS) analysis with bioinformatic filtering of a panel of genes known to cause intellectual disability and/or epileptic encephalopathies. Participants with no prior testing were first tested for mutations in MECP2 (Sanger sequencing and MLPA), and if the results of these tests were negative the exome-based HTS analysis was performed. During the diagnostic workup, the number of genes in the diagnostic gene panel for intellectual disability available from the laboratory increased from 45 to above 1400. When the number of genes increased the approach changed from a single patient analysis to a trio analysis with analyses of proband, father and mother. Seventy-four had a presumed pathological MECP2 mutation, and in four participants no pathological mutations were found.