Dendrimer-conjugated glutaminase inhibitor selectively targets microglial glutaminase in a mouse model of Rett syndrome
Conclusion: These findings demonstrate that glutaminase inhibitors conjugated to dendrimers are a viable mechanism to selectively inhibit microglial GLS to reduce glutamate production and improve mobility in a mouse model of RTT, with broader implications for selectively targeting this pathway in other neurodegenerative disorders. (Source: Theranostics)
Source: Theranostics - July 3, 2020 Category: Molecular Biology Authors: Elizabeth Smith Khoury, Anjali Sharma, Rajasekhar R Ramireddy, Ajit G. Thomas, Jesse Alt, Amanda Fowler, Rana Rais, Takashi Tsukamoto, Mary E. Blue, Barbara Slusher, Sujatha Kannan, Rangaramanujam M. Kannan Tags: Research Paper Source Type: research

The antitussive cloperastine improves breathing abnormalities in a Rett Syndrome mouse model by blocking presynaptic GIRK channels and enhancing GABA release.
Abstract Rett Syndrome (RTT) is an X-linked neurodevelopmental disorder caused mainly by mutations in the MECP2 gene. One of the major RTT features is breathing dysfunction characterized by periodic hypo- and hyperventilation. The breathing disorders are associated with increased brainstem neuronal excitability, which can be alleviated with antagonistic agents. Since neuronal hypoexcitability occurs in the forebrain of RTT models, it is necessary to find pharmacological agents with a relative preference to brainstem neurons. Here we show evidence for the improvement of breathing disorders of Mecp2-null mice with t...
Source: Neuropharmacology - July 2, 2020 Category: Drugs & Pharmacology Authors: Johnson CM, Cui N, Xing H, Wu Y, Jiang C Tags: Neuropharmacology Source Type: research

Cyclin-Dependent Kinase-Like 5 (CDKL5): Possible Cellular Signalling Targets and Involvement in CDKL5 Deficiency Disorder.
Abstract Cyclin-dependent kinase-like 5 (CDKL5, also known as STK9) is a serine/threonine protein kinase originally identified in 1998 during a transcriptional mapping project of the human X chromosome. Thereafter, a mutation in CDKL5 was reported in individuals with the atypical Rett syndrome, a neurodevelopmental disorder, suggesting that CDKL5 plays an important regulatory role in neuronal function. The disease associated with CDKL5 mutation has recently been recognised as CDKL5 deficiency disorder (CDD) and has been distinguished from the Rett syndrome owing to its symptomatic manifestation. Because CDKL5 muta...
Source: Neural Plasticity - June 28, 2020 Category: Neurology Authors: Katayama S, Sueyoshi N, Inazu T, Kameshita I Tags: Neural Plast Source Type: research

IJERPH, Vol. 17, Pages 4466: Challenges Affecting Access to Health and Social Care Resources and Time Management among Parents of Children with Rett Syndrome: A Qualitative Case Study
Domingo Palacios-Ceña Rare diseases face serious sustainability challenges regarding the distribution of resources geared at health and social needs. Our aim was to describe the barriers experienced by parents of children with Rett Syndrome for accessing care resources. A qualitative case study was conducted among 31 parents of children with Rett syndrome. Data were collected through in-depth interviews, focus groups, researchers’ field notes and parents’ personal documents. A thematic analysis was performed and the Standards for Reporting Qualitative Research (SRQR) guidelines were ...
Source: International Journal of Environmental Research and Public Health - June 21, 2020 Category: Environmental Health Authors: Javier G üeita-Rodriguez Pilar Famoso-P érez Jaime Salom-Moreno Pilar Carrasco-Garrido Jorge P érez-Corrales Domingo Palacios-Ce ña Tags: Article Source Type: research

Commentary: What matters most? Outcome measures in Rett syndrome
In the face of clinical and ethical obligations to improve quality of life for individuals with Rett syndrome (RTT), much research remains focused on functional impairments, despite RTT-specific domains of quality of life having recently been identified (12). The recent study by (5) critiques the design of the Rett Syndrome Behavioural Questionnaire (RSBQ) (8), its items, scales, domains and how these relate to clinical presentations of patients. The commentary in response from (9) is a critique of the sample used by (5) in their justification of refuting the RSBQ. (Source: Pediatric Neurology)
Source: Pediatric Neurology - June 20, 2020 Category: Neurology Authors: Brittany Mann Tags: Opinion Paper Source Type: research

WITHDRAWN: Commentary: What matters most? Outcome measures in Rett syndrome
This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause.The full Elsevier Policy on Article Withdrawal can be found athttps://www.elsevier.com/about/our-business/policies/article-withdrawal (Source: Pediatric Neurology)
Source: Pediatric Neurology - June 20, 2020 Category: Neurology Authors: Brittany Mann Source Type: research

GSE149094 Inhibition of BET proteins rescues neural defects in Rett syndrome [DNA methylation profile]
Contributors : Yangfei Xiang ; Yoshiaki Tanaka ; Eriona Hysolli ; In-Hyun ParkSeries Type : Methylation profiling by high throughput sequencingOrganism : Homo sapiensRett syndrome (RTT) is a severe X-linked neurodevelopmental disorder caused by mutations in the methyl-CpG binding protein 2 (MeCP2). Cellular heterogeneity in the brain confounds the understanding of RTT etiology. To date, how MeCP2 mutation affects defined cell types in human brain remains unclear, and effective therapeutics for RTT is lacking. Here we show that cell-type-specific transcriptome impairment and JQ1-mediated rescue in RTT cells from dorsal and ...
Source: GEO: Gene Expression Omnibus - June 12, 2020 Category: Genetics & Stem Cells Tags: Methylation profiling by high throughput sequencing Homo sapiens Source Type: research

GSE117513 Inhibition of BET proteins rescues neural defects in Rett syndrome
Series Type : Genome binding/occupancy profiling by high throughput sequencing ; Other ; Expression profiling by high throughput sequencing ; Methylation profiling by high throughput sequencingOrganism : Homo sapiensThis SuperSeries is composed of the SubSeries listed below. (Source: GEO: Gene Expression Omnibus)
Source: GEO: Gene Expression Omnibus - June 12, 2020 Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Other Expression profiling by high throughput sequencing Methylation profiling by high throughput sequencing Homo sapiens Source Type: research

GSE117512 Inhibition of BET proteins rescues neural defects in Rett syndrome [scRNA-seq]
Contributors : Yangfei Xiang ; Yoshiaki Tanaka ; Benjamin Patterson ; In-Hyun ParkSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensRett syndrome (RTT) is a severe X-linked neurodevelopmental disorder caused by mutations in the methyl-CpG binding protein 2 (MeCP2). Cellular heterogeneity in the brain confounds the understanding of RTT etiology. To date, how MeCP2 mutation affects defined cell types in human brain remains unclear, and effective therapeutics for RTT is lacking. Here we show that cell-type-specific transcriptome impairment and JQ1-mediated rescue in RTT cells from dorsal a...
Source: GEO: Gene Expression Omnibus - June 12, 2020 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research

GSE117511 Inhibition of BET proteins rescues neural defects in Rett syndrome [RNA-seq]
Contributors : Yangfei Xiang ; Yoshiaki Tanaka ; In-Hyun ParkSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensRett syndrome (RTT) is a severe X-linked neurodevelopmental disorder caused by mutations in the methyl-CpG binding protein 2 (MeCP2). Cellular heterogeneity in the brain confounds the understanding of RTT etiology. To date, how MeCP2 mutation affects defined cell types in human brain remains unclear, and effective therapeutics for RTT is lacking. Here we show that cell-type-specific transcriptome impairment and JQ1-mediated rescue in RTT cells from dorsal and ventral human fore...
Source: GEO: Gene Expression Omnibus - June 12, 2020 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research

GSE117509 Inhibition of BET proteins rescues neural defects in Rett syndrome [HiC-seq]
Contributors : Yangfei Xiang ; Yoshiaki Tanaka ; Benjamin Patterson ; In-Hyun ParkSeries Type : OtherOrganism : Homo sapiensRett syndrome (RTT) is a severe X-linked neurodevelopmental disorder caused by mutations in the methyl-CpG binding protein 2 (MeCP2). Cellular heterogeneity in the brain confounds the understanding of RTT etiology. To date, how MeCP2 mutation affects defined cell types in human brain remains unclear, and effective therapeutics for RTT is lacking. Here we show that cell-type-specific transcriptome impairment and JQ1-mediated rescue in RTT cells from dorsal and ventral human forebrain organoids. We find...
Source: GEO: Gene Expression Omnibus - June 12, 2020 Category: Genetics & Stem Cells Tags: Other Homo sapiens Source Type: research

GSE117508 Inhibition of BET proteins rescues neural defects in Rett syndrome [ChIP-seq]
Contributors : Yangfei Xiang ; Yoshiaki Tanaka ; In-Hyun ParkSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensRett syndrome (RTT) is a severe X-linked neurodevelopmental disorder caused by mutations in the methyl-CpG binding protein 2 (MeCP2). Cellular heterogeneity in the brain confounds the understanding of RTT etiology. To date, how MeCP2 mutation affects defined cell types in human brain remains unclear, and effective therapeutics for RTT is lacking. Here we show that cell-type-specific transcriptome impairment and JQ1-mediated rescue in RTT cells from dorsal and vent...
Source: GEO: Gene Expression Omnibus - June 12, 2020 Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Homo sapiens Source Type: research

GSE117507 Inhibition of BET proteins rescues neural defects in Rett syndrome [ATAC-seq]
Contributors : Yangfei Xiang ; Yoshiaki Tanaka ; In-Hyun ParkSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensRett syndrome (RTT) is a severe X-linked neurodevelopmental disorder caused by mutations in the methyl-CpG binding protein 2 (MeCP2). Cellular heterogeneity in the brain confounds the understanding of RTT etiology. To date, how MeCP2 mutation affects defined cell types in human brain remains unclear, and effective therapeutics for RTT is lacking. Here we show that cell-type-specific transcriptome impairment and JQ1-mediated rescue in RTT cells from dorsal and vent...
Source: GEO: Gene Expression Omnibus - June 12, 2020 Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Homo sapiens Source Type: research

Atypical processing of tones and phonemes in Rett Syndrome as biomarkers of disease progression
Translational Psychiatry, Published online: 10 June 2020; doi:10.1038/s41398-020-00877-4Atypical processing of tones and phonemes in Rett Syndrome as biomarkers of disease progression (Source: Translational Psychiatry)
Source: Translational Psychiatry - June 10, 2020 Category: Psychiatry Authors: Olga V. Sysoeva Sophie Molholm Aleksandra Djukic Hans-Peter Frey John J. Foxe Source Type: research

Assessment of a Clinical Trial Metric for Rett Syndrome: Critical Analysis of the Rett Syndrome Behavioural Questionnaire
The article by Hou et al. [1] evaluated item and score distributions and test-retest reliability for the Rett Syndrome Behaviour Questionnaire (RSBQ) [2] in 149 patients with Rett syndrome (RTT). The authors report that total, but not domain scores were normally distributed and Cronbach alpha values indicated good internal consistency. However, the scale had poor test-retest reliability and approximately half of the items exhibited floor or ceiling effects. (Source: Pediatric Neurology)
Source: Pediatric Neurology - June 2, 2020 Category: Neurology Authors: Lindsay M. Oberman, Jenny Downs, Helen Leonard, Rina Cianfaglione, Walter E. Kaufmann Tags: Correspondence Source Type: research

Proteomic profiling reveals mitochondrial alterations in Rett syndrome.
In conclusion, our proteomic analysis confirms the pathological relevance of mitochondrial dysfunction in RTT pathogenesis and progression. PMID: 32445864 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - May 20, 2020 Category: Biology Authors: Cicaloni V, Pecorelli A, Tinti L, Rossi M, Benedusi M, Cervellati C, Spiga O, Santucci A, Hayek J, Salvini L, Tinti C, Valacchi G Tags: Free Radic Biol Med Source Type: research

MeCP2 in cholinergic interneurons of nucleus accumbens regulates fear learning
Methyl-CpG-binding protein 2 (MeCP2) encoded by theMECP2 gene is a transcriptional regulator whose mutations cause Rett syndrome (RTT).Mecp2-deficient mice show fear regulation impairment; however, the cellular and molecular mechanisms underlying this abnormal behavior are largely uncharacterized. Here, we showed thatMecp2 gene deficiency in cholinergic interneurons of the nucleus accumbens (NAc) dramatically impaired fear learning. We further found that spontaneous activity of cholinergic interneurons inMecp2-deficient mice decreased, mediated by enhanced inhibitory transmission via α2-containing GABAA receptors. Wi...
Source: eLife - May 18, 2020 Category: Biomedical Science Tags: Neuroscience Source Type: research

Neurochemistry of the K ölliker‐Fuse nucleus from a respiratory perspective
AbstractThe K ölliker‐Fuse nucleus (KF) is a functionally distinct component of the parabrachial complex, located in the dorsolateral pons of mammals. The KF has a major role in respiration and upper airway control. A comprehensive understanding of the KF and its contributions to respiratory function and dysfu nction requires an appreciation for its neurochemical characteristics. The goal of this review is to summarize the diverse neurochemical composition of the KF, focusing on the neurotransmitters, neuromodulators and neuropeptides present. We also include a description of the receptors expressed on KF neurons an...
Source: Journal of Neurochemistry - May 12, 2020 Category: Neuroscience Authors: Adrienn G. Varga, Sebastian N. Maletz, Jordan T. Bateman, Brandon T. Reid, Erica S. Levitt Tags: REVIEW ARTICLE Source Type: research

Three intellectual disability-associated de novo mutations in MECP2 identified by trio-WES analysis
To date, at least 746 genes have been identified to cause intellectual disability (ID). Among them, mutations in the Methyl CpG binding protein 2 (MECP2) gene are the leading cause of Rett syndrome and associated... (Source: BMC Medical Genetics)
Source: BMC Medical Genetics - May 11, 2020 Category: Genetics & Stem Cells Authors: Yi Gu, Bingwu Xiang, Lina Zhu, Xiuwei Ma, Xiang Chen and Tao Cai Tags: Research article Source Type: research

Detection of Rare Methyl-CpG Binding Protein 2 Gene Missense Mutations in Patients With Schizophrenia
Deleterious mutations of MECP2 are responsible for Rett syndrome, a severe X-linked childhood neurodevelopmental disorder predominates in females, male patients are considered fatal. However, increasing reports indicate that some MECP2 mutations may also present various neuropsychiatric phenotypes, including intellectual disability, autism spectrum disorder, depression, cocaine addiction, and schizophrenia in both males and females, suggesting varied clinical expressivity in some MECP2 mutations. Most of the MECP2 mutations are private de novo mutations. To understand whether MECP2 mutations are associated with schizophren...
Source: Frontiers in Genetics - May 8, 2020 Category: Genetics & Stem Cells Source Type: research

Developmental loss of MeCP2 from VIP interneurons impairs cortical function and behavior
Rett Syndrome is a devastating neurodevelopmental disorder resulting from mutations in the geneMECP2. Mutations ofMecp2restricted to GABAergic cell types largely replicate the behavioral phenotypes associated with mouse models of Rett Syndrome, suggesting a pathophysiological role for inhibitory interneurons. Recent work has suggested that vasoactive intestinal peptide-expressing (VIP) interneurons may play a critical role in the proper development and function of cortical circuits, making them a potentially key point of vulnerability in neurodevelopmental disorders. However, little is known about the role of VIP interneur...
Source: eLife - April 28, 2020 Category: Biomedical Science Tags: Neuroscience Source Type: research

Suppressor mutations in Mecp2-null mice implicate the DNA damage response in Rett syndrome pathology [RESEARCH]
Mutations in X-linked methyl-CpG-binding protein 2 (MECP2) cause Rett syndrome (RTT). To identify functional pathways that could inform therapeutic entry points, we carried out a genetic screen for secondary mutations that improved phenotypes in Mecp2/Y mice after mutagenesis with N-ethyl-N-nitrosourea (ENU). Here, we report the isolation of 106 founder animals that show suppression of Mecp2-null traits from screening 3177 Mecp2/Y genomes. Whole-exome sequencing, genetic crosses, and association analysis identified 22 candidate genes. Additional lesions in these candidate genes or pathway components associate variant allel...
Source: Genome Research - April 27, 2020 Category: Genetics & Stem Cells Authors: Enikanolaiye, A., Ruston, J., Zeng, R., Taylor, C., Schrock, M., Buchovecky, C. M., Shendure, J., Acar, E., Justice, M. J. Tags: RESEARCH Source Type: research

Genetic and clinical variations in a Norwegian sample diagnosed with Rett syndrome
Rett syndrome (RTT) is a neurodevelopmental disorder mainly caused by mutations in MECP2. The diagnostic criteria of RTT are clinical; mutations in MECP2 are neither diagnostic nor necessary, and a mutation in another gene does not exclude RTT. We attempted to correlate genotype and phenotype to see if there are significant clinical associations. (Source: Brain and Development)
Source: Brain and Development - April 23, 2020 Category: Neurology Authors: Mari Wold Henriksen, Hilde Breck, Yngve Sejersted, Trond Diseth, Stephen von Tetzchner, Benedicte Paus, Ola H. Skjeldal Tags: Original article Source Type: research

Suppressor mutations in Mecp2-null mice implicate the DNA damage response in Rett syndrome pathology [RESEARCH]
Mutations in X-linked methyl-CpG-binding protein 2 (MECP2) cause Rett syndrome (RTT). To identify functional pathways that could inform therapeutic entry points, we carried out a genetic screen for secondary mutations that improved phenotypes in Mecp2/Y mice after mutagenesis with N-ethyl-N-nitrosourea (ENU). Here, we report the isolation of 106 founder animals that show suppression of Mecp2-null traits from screening 3177 Mecp2/Y genomes. Whole-exome sequencing, genetic crosses, and association analysis identified 22 candidate genes. Additional lesions in these candidate genes or pathway components associate variant allel...
Source: Genome Research - April 21, 2020 Category: Genetics & Stem Cells Authors: Enikanolaiye, A., Ruston, J., Zeng, R., Taylor, C., Schrock, M., Buchovecky, C. M., Shendure, J., Acar, E., Justice, M. J. Tags: RESEARCH Source Type: research

Defective proteasome biogenesis into skin fibroblasts isolated from Rett syndrome subjects with MeCP2 non-sense mutations
Publication date: Available online 8 April 2020Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Diego Sbardella, Grazia Raffaella Tundo, Vincenzo Cunsolo, Giuseppe Grasso, Raffaella Cascella, Valerio Caputo, Anna Maria Santoro, Danilo Milardi, Alessandra Pecorelli, Chiara Ciaccio, Donato Di Pierro, Silvia Leoncini, Luisa Campagnolo, Virginia Pironi, Francesco Oddone, Priscilla Manni, Salvatore Foti, Emiliano Giardina, Claudio De Felice, Joussef Hayek (Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease)
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - April 8, 2020 Category: Molecular Biology Source Type: research

Shifts in Ribosome Engagement Impact Key Gene Sets in Neurodevelopment and Ubiquitination in Rett Syndrome
Publication date: 24 March 2020Source: Cell Reports, Volume 30, Issue 12Author(s): Deivid C. Rodrigues, Marat Mufteev, Robert J. Weatheritt, Ugljesa Djuric, Kevin C.H. Ha, P. Joel Ross, Wei Wei, Alina Piekna, Maria A. Sartori, Loryn Byres, Rebecca S.F. Mok, Kirill Zaslavsky, Peter Pasceri, Phedias Diamandis, Quaid Morris, Benjamin J. Blencowe, James Ellis (Source: Cell Reports)
Source: Cell Reports - March 26, 2020 Category: Cytology Source Type: research

The multiple facets of the SMC1A gene.
Abstract Structural Maintenance of Chromosomes (SMCs) are part of a large family of ring complexes that participates in a number of DNA transactions. Among SMCs, SMC1A gene is unique. It encodes a subunit of the cohesin-core complex that tethers sister chromatids together to ensure correct chromosome segregation in both mitosis and meiosis. As a member of the cohesin ring, SMC1A takes part in gene transcription regulation and genome organization; and it participates in the DNA Damage Repair (DDR) pathway, being phosphorylated by Ataxia Telangiectasia Mutated (ATM) and Ataxia Telangiectasia and Rad3 Related (ATR) t...
Source: Gene - March 25, 2020 Category: Genetics & Stem Cells Authors: Musio A Tags: Gene Source Type: research

Whole brain delivery of an instability-prone < i > Mecp2 < /i > transgene improves behavioral and molecular pathological defects in mouse models of Rett syndrome
Rett syndrome is an incurable neurodevelopmental disorder caused by mutations in the gene encoding for methyl-CpG binding-protein 2 (MeCP2). Gene therapy for this disease presents inherent hurdles sinceMECP2 is expressed throughout the brain and its duplication leads to severe neurological conditions as well. Herein, we use the AAV-PHP.eB to deliver an instability-proneMecp2 (iMecp2) transgene cassette which, increasing RNA destabilization and inefficient protein translation of the viralMecp2transgene, limits supraphysiological Mecp2 protein levels. Intravenous injections of the PHP.eB-iMecp2 virus in symptomaticMecp2 muta...
Source: eLife - March 24, 2020 Category: Biomedical Science Tags: Neuroscience Source Type: research

Hidradenitis suppurativa in a female adolescent with Rett syndrome: a fortuitous association?
Authors: Provvidenziale L, Cinotti E, Campoli M, Russo F, Rubegni P PMID: 32163043 [PubMed - as supplied by publisher] (Source: Giornale Italiano di Dermatologia e Venereologia)
Source: Giornale Italiano di Dermatologia e Venereologia - March 14, 2020 Category: Dermatology Tags: G Ital Dermatol Venereol Source Type: research

Losing Dnmt3a dependent methylation in inhibitory neurons impairs neural function by a mechanism impacting Rett syndrome
Methylated cytosine is an effector of epigenetic gene regulation. In the brain, Dnmt3a is the sole ‘writer’ of atypical non-CpG methylation (mCH), and MeCP2 is the only known ‘reader’ for mCH. We asked if MeCP2 is the sole reader for Dnmt3a dependent methylation by comparing mice lacking either protein in GABAergic inhibitory neurons. Loss of either protein causes overlapping and distinct features from the behavioral to molecular level. Loss of Dnmt3a causes global loss of mCH and a subset of mCG sites resulting in more widespread transcriptional alterations and severe neurological dysfunction than ...
Source: eLife - March 11, 2020 Category: Biomedical Science Tags: Chromosomes and Gene Expression Neuroscience Source Type: research

Mild presentation of the congenital variant Rett syndrome in a Pakistani male: expanding the phenotype of the forkhead box protein G1 spectrum
No abstract available (Source: Clinical Dysmorphology)
Source: Clinical Dysmorphology - March 10, 2020 Category: Genetics & Stem Cells Tags: Short Case Reports Source Type: research

Sleep Quality in Children and Adults with Rett Syndrome
Conclusion Our study showed sleep dysfunction to be less prevalent in RTT-affected individuals than evidence from past studies has suggested. Nevertheless, this remains a subjective assessment of sleep quality and therefore the need to find objective, disorder-specific parameters that measure sleep quality in RTT patients persists. [...] Georg Thieme Verlag KG Stuttgart · New YorkArticle in Thieme eJournals: Table of contents  |  Abstract  |  Full text (Source: Neuropediatrics)
Source: Neuropediatrics - March 6, 2020 Category: Neurology Authors: Leven, Y. Wiegand, F. Wilken, B. Tags: Original Article Source Type: research

Compromised immune/inflammatory responses in Rett syndrome.
Abstract Mutations in X-linked gene methyl-CpG-binding protein 2 (MECP2), a key transcriptional regulator, account for most cases of Rett syndrome (RTT), a devastating neurodevelopmental disorder with no known cure. Despite extensive research to elucidate MeCP2 functions, the mechanisms underlying RTT pathophysiology are still unclear. In addition to a variety of neurological symptoms, RTT also includes a plethora of additional phenotypical features including altered lipid metabolism, redox imbalance, immune dysfunction and mitochondrial abnormalities that explain its multisystemic nature. Here, we provide an over...
Source: Free Radical Biology and Medicine - February 28, 2020 Category: Biology Authors: Pecorelli A, Cervellati C, Cordone V, Hayek J, Valacchi G Tags: Free Radic Biol Med Source Type: research

Rett Syndrome, a Neurodevelopmental Disorder, Whole-Transcriptome, and Mitochondrial Genome Multiomics Analyses Identify Novel Variations and Disease Pathways
OMICS: A Journal of Integrative Biology, Ahead of Print. (Source: OMICS: A Journal of Integrative Biology)
Source: OMICS: A Journal of Integrative Biology - February 27, 2020 Category: Biology Authors: Mazhor Aldosary AlBandary Al-Bakheet Hesham Al-Dhalaan Rawan Almass Maysoon Alsagob Banan Al-Younes Laila AlQuait Osama Mufid Mustafa Mustafa Bulbul Zuhair Rahbeeni Majid Alfadhel Aziza Chedrawi Zuhair Al-Hassnan Mohammed AlDosari Hamad Al-Zaidan Mohammad Source Type: research

Difficult airway in a paediatric Rett Syndrome – a challenge outside the Operating Room
Publication date: February 2020Source: Trends in Anaesthesia and Critical Care, Volume 30Author(s): Joana Veiga, Sara Alves, Marta Gonçalves, Helena Salgado (Source: Trends in Anaesthesia and Critical Care)
Source: Trends in Anaesthesia and Critical Care - February 25, 2020 Category: Anesthesiology Source Type: research

MeCP2 is involved in random mono-allelic expression for a subset of human autosomal genes
Publication date: Available online 15 February 2020Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Marine Brousseau, Juliette Nectoux, Benjamin Saintpierre, Nicolas Lebrun, Nicolas Cagnard, Brigitte Izac, Emmanuelle Olivier, Franck Letourneur, Thierry BienvenuAbstractWidespread random monoallelic gene expression (RMAE) effects influence about 10% of human genes. However, the mechanisms by which RME of autosomal genes is established and those by which it is maintained both remain open questions. Because the choice of allelic expression is randomly performed cell-by-cell, the RMAE mechanism...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - February 17, 2020 Category: Molecular Biology Source Type: research

Seizures in Mouse Models of Rare Neurodevelopmental Disorders
Publication date: Available online 12 February 2020Source: NeuroscienceAuthor(s): Merrick S. Fallah, James H. EubanksAbstractGenetic neurodevelopmental disorders that often include epilepsy as part of their phenotype are a heterogeneous and clinically challenging spectrum of disorders in children. Although seizures often contribute significantly to morbidity in these affected populations, the mechanisms of epileptogenesis in these conditions remain poorly understood. Different model systems have been developed to aid unraveling these mechanisms, which include a number of specific mutant mouse lines which genocopy specific ...
Source: Neuroscience - February 13, 2020 Category: Neuroscience Source Type: research

Assessment of a Clinical Trial Metric for Rett Syndrome: Critical Analysis of the Rett Syndrome Behavioural Questionnaire
We examined the merits and flaws of the Rett Syndrome Behavioural Questionnaire (RSBQ) as an outcome measure for clinical trials. (Source: Pediatric Neurology)
Source: Pediatric Neurology - February 4, 2020 Category: Neurology Authors: Wei Hou, Usree Bhattacharya, Wisnu A. Pradana, Daniel C. Tarquinio Tags: Research Paper Source Type: research

Twenty years of research on the DFS70/LEDGF autoantibody-autoantigen system: many lessons learned but still many questions
AbstractThe discovery and initial characterization 20  years ago of antinuclear autoantibodies (ANAs) presenting a dense fine speckled (DFS) nuclear pattern with strong staining of mitotic chromosomes, detected by indirect immunofluorescence assay in HEp-2 cells (HEp-2 IIFA test), has transformed our view on ANAs. Traditionally, ANAs have been conside red as reporters of abnormal immunological events associated with the onset and progression of systemic autoimmune rheumatic diseases (SARD), also called ANA-associated rheumatic diseases (AARD), as well as clinical biomarkers for the differential diagnosis of these dise...
Source: Autoimmunity Highlights - February 3, 2020 Category: Allergy & Immunology Source Type: research

Special Education Supports and Services for Rett Syndrome: Parent Perceptions and Satisfaction
Intellectual and Developmental Disabilities,Volume 58, Issue 1, Page 49-64, February 2020. (Source: Intellectual and Developmental Disabilities)
Source: Intellectual and Developmental Disabilities - February 3, 2020 Category: Disability Authors: Kelsey Larriba-Quest Breanne J. Byiers Arthur Beisang Alyssa M. Merbler Frank J. Symons Source Type: research

Drug Studies on Rett Syndrome: From Bench to Bedside.
Abstract Drug studies on Rett syndrome (RTT) have drastically increased over the past few decades. This review aims to provide master data on bench-to-bedside drug studies involving RTT. A comprehensive literature review was performed by searching in PUBMED, MEDLINE and Google Scholar, international, national and regional clinical trial registries and pharmaceutical companies using the keywords "Rett syndrome treatment and/or drug or compound or molecule". Seventy drugs were investigated in non-clinical (N = 65 animal/cell line-based studies; N = 5 iPSC-based study) and clinic...
Source: Journal of Autism and Developmental Disorders - February 3, 2020 Category: Psychiatry Authors: Gomathi M, Padmapriya S, Balachandar V Tags: J Autism Dev Disord Source Type: research

Special Education Supports and Services for Rett Syndrome: Parent Perceptions and Satisfaction
Intellectual and Developmental Disabilities,Volume 58, Issue 1, Page 49-64, February 2020. (Source: Intellectual and Developmental Disabilities)
Source: Intellectual and Developmental Disabilities - February 3, 2020 Category: Disability Authors: Kelsey Larriba-Quest Breanne J. Byiers Arthur Beisang Alyssa M. Merbler Frank J. Symons Source Type: research

Methyl-CpG-binding protein 2 (MECP2) mutation type is associated with bone disease severity in Rett syndrome
More than 95% of individuals with RTT have mutations in methyl-CpG-binding protein 2 (MECP2), whose protein product modulates gene transcription. The disorder is caused by mutations in a single gene and the di... (Source: BMC Medical Genetics)
Source: BMC Medical Genetics - January 31, 2020 Category: Genetics & Stem Cells Authors: Carla Caffarelli, Stefano Gonnelli, Maria Dea Tomai Pitinca, Silvia Camarri, Antonella Al Refaie, Joussef Hayek and Ranuccio Nuti Tags: Research article Source Type: research

De novo variants in the Helicase-C domain of CHD8 are associated with severe phenotypes including autism, language disability and overgrowth
AbstractCHD8, which encodes Chromodomain helicase DNA-binding protein 8, is one of a few well-established Autism Spectrum Disorder (ASD) genes. Over 60 mutations have been reported in subjects with variable phenotypes, but little is known concerning genotype –phenotype correlations. We have identified four novel de novo mutations in Chinese subjects: two nonsense variants (c.3562C>T/p.Arg1188X, c.2065C>A/p.Glu689X), a splice site variant (c.4818-1G>A) and a missense variant (c.3502T>A/p.Tyr1168Asn). Three of these were identified from a 445-member ASD cohort by ASD gene panel sequencing of the 96 subjects...
Source: Human Genetics - January 24, 2020 Category: Genetics & Stem Cells Source Type: research

The effect of fornix deep brain stimulation in brain diseases.
Abstract Deep brain stimulation is used to alleviate symptoms of neurological and psychiatric disorders including Parkinson's disease, epilepsy, and obsessive-compulsive-disorder. Electrically stimulating limbic structures has been of great interest, and in particular, the region of the fornix. We conducted a systematic search for studies that reported clinical and preclinical outcomes of deep brain stimulation within the fornix up to July 2019. We identified 13 studies (7 clinical, 6 preclinical) that examined the effects of fornix stimulation in Alzheimer's disease (n = 9), traumatic brain injury (...
Source: Cellular and Molecular Life Sciences : CMLS - January 23, 2020 Category: Cytology Authors: Liu H, Temel Y, Boonstra J, Hescham S Tags: Cell Mol Life Sci Source Type: research

Two novel mutations in the MECP2 gene in patients with Rett syndrome.
In this study, we report the results of screening the MECP2 gene for mutations in 7 Iranian patients with RTT syndrome. MECP2 sequencing identified two novel mutations in the heterozygous state, a splice mutation, c.354G>T, p.Gly119Gly, resulting in a premature splice-donor site and a 20-bp deletion, c.1167-1186del20 (p.P390Rfs), leading to modifying the c-terminal parts of the protein and it also changes the reading frames of all coding sequence downstream of the mutation. Multiple sequence alignment showed that amino acid changes occurred in the well conserved protein regions across species. Based on the results of th...
Source: Gene - January 17, 2020 Category: Genetics & Stem Cells Authors: Khalili Alashti S, Fallahi J, Mohammadi S, Dehghanian F, Farbood Z, Masoudi M, Poorang S, Jokar A, Fardaei M Tags: Gene Source Type: research

Jumonji domain containing 1C (JMJD1C) sequence variants in seven patients with autism spectrum disorder, intellectual disability and seizures.
We report seven, unrelated patients with developmental delays or intellectual disability and heterozygous, de novo sequence variants in JMJD1C. All patients had developmental delays, but there were no consistent additional findings. Two patients were reported to have seizures for which there was no other identified cause. De novo, deleterious sequence variants in JMJD1C have previously been reported in patients with autism spectrum disorder and a phenotype resembling classical Rett syndrome, but only one JMJD1C variant has undergone functional evaluation. In all of the seven patients in this report, there was a plausible, ...
Source: European Journal of Medical Genetics - January 16, 2020 Category: Genetics & Stem Cells Authors: Slavotinek A, van Hagen JM, Kalsner L, Pai S, Davis-Keppen L, Ohden L, Weber YG, Macke EL, Klee EW, Morava E, Gunderson L, Person R, Liu S, Weiss M Tags: Eur J Med Genet Source Type: research

Atypical Rett syndrome in a girl with mosaic triple X and MECP2 variant
ConclusionThe present results indicate that phenotypic effects of X chromosome aneuploidy depend on the nature of the supernumerary X chromosome, the pattern of mosaicism, and XCI status. (Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - January 13, 2020 Category: Genetics & Stem Cells Authors: Satoru Takahashi, Ryo Takeguchi, Mami Kuroda, Ryosuke Tanaka Tags: CLINICAL REPORT Source Type: research

Rett syndrome: the Brazilian contribution to the gene discovery
ABSTRACT A brief history of the syndrome discovered by Andreas Rett is reported in this paper. Although having been described in 1966, the syndrome was only recognized by the international community after a report by Hagberg et al. in 1983. Soon, its importance was evident as a relatively frequent cause of severe encephalopathy among girls. From the beginning it was difficult to explain the absence of male patients and the almost total predominance of sporadic cases (99%), with very few familial cases. For these reasons, it was particularly difficult to investigate this condition until 1997, when a particular Brazilian fam...
Source: Arquivos de Neuro-Psiquiatria - January 10, 2020 Category: Neurology Source Type: research

Aberrantly High Levels of Somatic LINE-1 Expression and Retrotransposition in Human Neurological Disorders
Retrotransposable elements (RTEs) have actively multiplied over the past 80 million years of primate evolution, and as a consequence, such elements collectively occupy ∼ 40% of the human genome. As RTE activity can have detrimental effects on the human genome and transcriptome, silencing mechanisms have evolved to restrict retrotransposition. The brain is the only known somatic tissue where RTEs are de-repressed throughout the life of a healthy human and each neuron in specific brain regions accumulates up to ∼13.7 new somatic L1 insertions (and perhaps more). However, even higher levels of somatic RTE expression a...
Source: Frontiers in Genetics - January 8, 2020 Category: Genetics & Stem Cells Source Type: research