{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T15:50:08Z","timestamp":1776786608220,"version":"3.51.2"},"reference-count":69,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T00:00:00Z","timestamp":1663804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Trustee for the Neil &amp; Norma Hill Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Rett syndrome (RTT) is a rare disorder and one of the most abundant causes of intellectual disabilities in females. Single mutations in the gene coding for methyl-CpG-binding protein 2 (MeCP2) are responsible for the disorder. MeCP2 regulates gene expression as a transcriptional regulator as well as through epigenetic imprinting and chromatin condensation. Consequently, numerous biological pathways on multiple levels are influenced. However, the exact molecular pathways from genotype to phenotype are currently not fully elucidated. Treatment of RTT is purely symptomatic as no curative options for RTT have yet to reach the clinic. The paucity of this is mainly due to an incomplete understanding of the underlying pathophysiology of the disorder with no clinically useful common disease drivers, biomarkers, or therapeutic targets being identified. With the premise of identifying universal and robust disease drivers and therapeutic targets, here, we interrogated a range of RTT transcriptomic studies spanning different species, models, and MECP2 mutations. A meta-analysis using RNA sequencing data from brains of RTT mouse models, human post-mortem brain tissue, and patient-derived induced pluripotent stem cell (iPSC) neurons was performed using weighted gene correlation network analysis (WGCNA). This study identified a module of genes common to all datasets with the following ten hub genes driving the expression: ATRX, ADCY7, ADCY9, SOD1, CACNA1A, PLCG1, CCT5, RPS9, BDNF, and MECP2. Here, we discuss the potential benefits of these genes as therapeutic targets.<\/jats:p>","DOI":"10.3390\/ijms231911125","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T05:33:14Z","timestamp":1663824794000},"page":"11125","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Meta-Analysis Identifies BDNF and Novel Common Genes Differently Altered in Cross-Species Models of Rett Syndrome"],"prefix":"10.3390","volume":"23","author":[{"given":"Florencia","family":"Haase","sequence":"first","affiliation":[{"name":"School of Medical Science, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia"},{"name":"Kids Neuroscience Centre, Kids Research, Children\u2019s Hospital at Westmead, Westmead, NSW 2145, Australia"},{"name":"Molecular Neurobiology Research Laboratory, Kids Research, Children\u2019s Hospital at Westmead, Westmead, NSW 2145, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2540-2044","authenticated-orcid":false,"given":"Rachna","family":"Singh","sequence":"additional","affiliation":[{"name":"School of Medicine Sydney, The University of Notre Dame, Chippendale, NSW 2007, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Gloss","sequence":"additional","affiliation":[{"name":"Westmead Research Hub, Westmead Institute for Medical Research, Westmead, NSW 2145, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6950-8388","authenticated-orcid":false,"given":"Patrick","family":"Tam","sequence":"additional","affiliation":[{"name":"School of Medical Science, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia"},{"name":"Embryology Research Unit, Children\u2019s Medical Research Institute, The University of Sydney, Camperdown, NSW 2006, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1808-0646","authenticated-orcid":false,"given":"Wendy","family":"Gold","sequence":"additional","affiliation":[{"name":"School of Medical Science, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia"},{"name":"Kids Neuroscience Centre, Kids Research, Children\u2019s Hospital at Westmead, Westmead, NSW 2145, Australia"},{"name":"Molecular Neurobiology Research Laboratory, Kids Research, Children\u2019s Hospital at Westmead, Westmead, NSW 2145, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1002\/ana.22124","article-title":"Rett syndrome: Revised diagnostic criteria and nomenclature","volume":"68","author":"Neul","year":"2010","journal-title":"Ann. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"593554","DOI":"10.3389\/fneur.2020.593554","article-title":"Loss of MeCP2 Function Across Several Neuronal Populations Impairs Breathing Response to Acute Hypoxia","volume":"11","author":"Ward","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5085","DOI":"10.1093\/nar\/20.19.5085","article-title":"Characterization of MeCP2, a vertebrate DNA binding protein with affinity for methylated DNA","volume":"20","author":"Meehan","year":"1992","journal-title":"Nucleic Acids Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/nature14319","article-title":"Disruption of DNA-methylation-dependent long gene repression in Rett syndrome","volume":"522","author":"Gabel","year":"2015","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/nn.3607","article-title":"Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain","volume":"17","author":"Guo","year":"2014","journal-title":"Nat. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"118","DOI":"10.3389\/fncir.2013.00118","article-title":"The first mecp2-null zebrafish model shows altered motor behaviors","volume":"7","author":"Pietri","year":"2013","journal-title":"Front. Neural Circuits"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1126\/science.1153252","article-title":"MeCP2, a Key Contributor to Neurological Disease, Activates and Represses Transcription","volume":"320","author":"Chahrour","year":"2008","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"17551","DOI":"10.1073\/pnas.0507856102","article-title":"Regulation of RNA splicing by the methylation-dependent transcriptional repressor methyl-CpG binding protein 2","volume":"102","author":"Young","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.molcel.2019.10.032","article-title":"MeCP2 Represses the Rate of Transcriptional Initiation of Highly Methylated Long Genes","volume":"77","author":"Boxer","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"825063","DOI":"10.3389\/fnins.2022.825063","article-title":"Excitation and Inhibition Imbalance in Rett Syndrome","volume":"16","author":"Li","year":"2022","journal-title":"Front. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.1002\/humu.23887","article-title":"Genome-wide transcriptomic and proteomic studies of Rett syndrome mouse models identify common signaling pathways and cellular functions as potential therapeutic targets","volume":"40","author":"Krishnaraj","year":"2019","journal-title":"Hum. Mutat."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1111\/j.1469-7580.2010.01281.x","article-title":"Renewed focus on the developing human neocortex","volume":"217","author":"Clowry","year":"2010","journal-title":"J. Anat."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.cell.2011.05.034","article-title":"The human brain in a dish: The promise of iPSC-derived neurons","volume":"145","author":"Dolmetsch","year":"2011","journal-title":"Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.cell.2010.10.016","article-title":"A Model for Neural Development and Treatment of Rett Syndrome Using Human Induced Pluripotent Stem Cells","volume":"143","author":"Marchetto","year":"2010","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.cell.2006.07.024","article-title":"Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors","volume":"126","author":"Takahashi","year":"2006","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.stem.2012.05.005","article-title":"Induced Pluripotent Stem Cells: Past, Present, and Future","volume":"10","author":"Yamanaka","year":"2012","journal-title":"Cell Stem Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1007\/s12015-018-9851-8","article-title":"Generation of Isogenic Controls for In Vitro Disease Modelling of X-Chromosomal Disorders","volume":"15","author":"Hinz","year":"2019","journal-title":"Stem Cell Rev. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1002\/cne.22009","article-title":"Widespread changes in dendritic and axonal morphology in Mecp2-mutant mouse models of rett syndrome: Evidence for disruption of neuronal networks","volume":"514","author":"Belichenko","year":"2009","journal-title":"J. Comp. Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Trujillo, C., Gao, R., Negraes, P., Chaim, I., Domissy, A., Vandenberghe, M., Devor, A., Yeo, G., Voytek, B., and Muotri, A. (2018). Nested oscillatory dynamics in cortical organoids model early human brain network development. bioRxiv.","DOI":"10.1101\/358622"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kim, J.J., Savas, J.N., Miller, M.T., Hu, X., Carromeu, C., Lavall\u00e9e-Adam, M., Freitas, B.C.G., Muotri, A.R., Yates, J.R., and Ghosh, A. (2019). Proteomic analyses reveal misregulation of LIN28 expression and delayed timing of glial differentiation in human iPS cells with MECP2 loss-of-function. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0212553"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"14169","DOI":"10.1073\/pnas.1018979108","article-title":"Neuronal maturation defect in induced pluripotent stem cells from patients with Rett syndrome","volume":"108","author":"Kim","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","first-page":"270","article-title":"IGF1 neuronal response in the absence of MECP2 is dependent on TRalpha 3","volume":"26","author":"Carromeu","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.celrep.2016.09.049","article-title":"MECP2 Is Post-transcriptionally Regulated during Human Neurodevelopment by Combinatorial Action of RNA-Binding Proteins and miRNAs","volume":"17","author":"Rodrigues","year":"2016","journal-title":"Cell Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/85906","article-title":"Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice","volume":"27","author":"Chen","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"105235","DOI":"10.1016\/j.nbd.2020.105235","article-title":"Severe offtarget effects following intravenous delivery of AAV9-MECP2 in a female mouse model of Rett syndrome","volume":"149","author":"Matagne","year":"2021","journal-title":"Neurobiol. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"R89","DOI":"10.1093\/hmg\/ddaa154","article-title":"Regulation, diversity and function of MECP2 exon and 3\u2019UTR isoforms","volume":"29","author":"Rodrigues","year":"2020","journal-title":"Hum. Mol. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13229-017-0174-4","article-title":"RNA sequencing and proteomics approaches reveal novel deficits in the cortex of Mecp2-deficient mice, a model for Rett syndrome","volume":"8","author":"Pacheco","year":"2017","journal-title":"Mol. Autism"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nbd.2016.12.009","article-title":"A codon-optimized Mecp2 transgene corrects breathing deficits and improves survival in a mouse model of Rett syndrome","volume":"99","author":"Matagne","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1016\/j.stemcr.2018.04.001","article-title":"Loss of MECP2 leads to activation of P53 and neuronal senescence","volume":"10","author":"Ohashi","year":"2018","journal-title":"Stem Cell Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"725398","DOI":"10.3389\/fnins.2021.725398","article-title":"Brain-Derived Neurotrophic Factor Secreting Human Mesenchymal Stem Cells Improve Outcomes in Rett Syndrome Mouse Models","volume":"15","author":"Kim","year":"2021","journal-title":"Front. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.neuron.2006.01.014","article-title":"The Ups and Downs of BDNF in Rett Syndrome","volume":"49","author":"Sun","year":"2006","journal-title":"Neuron"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.mito.2014.02.012","article-title":"Mitochondrial dysfunction in the skeletal muscle of a mouse model of Rett syndrome (RTT): Implications for the disease phenotype","volume":"15","author":"Gold","year":"2014","journal-title":"Mitochondrion"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"170216","DOI":"10.1098\/rsob.170216","article-title":"Rett syndrome: A neurological disorder with metabolic components","volume":"8","author":"Kyle","year":"2018","journal-title":"Open Biol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Marano, D., Fioriniello, S., Fiorillo, F., Gibbons, R.J., D\u2019Esposito, M., and Della Ragione, F. (2019). ATRX Contributes to MeCP2-Mediated Pericentric Heterochromatin Organization during Neural Differentiation. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20215371"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/0092-8674(95)90287-2","article-title":"Mutations in a putative global transcriptional regulator cause X-linked mental retardation with \u03b1-thalassemia (ATR-X syndrome)","volume":"80","author":"Gibbons","year":"1995","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.1073\/pnas.0608056104","article-title":"Interaction between chromatin proteins MECP2 and ATRX is disrupted by mutations that cause inherited mental retardation","volume":"104","author":"Nan","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Valenzuela, M., Amato, R., Sgura, A., Antoccia, A., and Berardinelli, F. (2021). The Multiple Facets of ATRX Protein. Cancers, 13.","DOI":"10.3390\/cancers13092211"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.ccell.2015.08.003","article-title":"Loss of ATRX Suppresses Resolution of Telomere Cohesion to Control Recombination in ALT Cancer Cells","volume":"28","author":"Ramamoorthy","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Kim, N., Kim, K.H., Lim, W.-J., Kim, J., Kim, S.A., and Yoo, H.J. (2020). Whole Exome Sequencing Identifies Novel De Novo Variants Interacting with Six Gene Networks in Autism Spectrum Disorder. Genes, 12.","DOI":"10.3390\/genes12010001"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"253","DOI":"10.31887\/DCNS.2012.14.3\/jneul","article-title":"The relationship of Rett syndrome and MECP2 disorders to autism","volume":"14","author":"Neul","year":"2012","journal-title":"Dialog. Clin. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1001\/archneurol.2011.149","article-title":"Rett syndrome: Exploring the autism link","volume":"68","author":"Percy","year":"2011","journal-title":"Arch. Neurol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s12987-022-00322-2","article-title":"Expression and functions of adenylyl cyclases in the CNS","volume":"19","author":"Devasani","year":"2022","journal-title":"Fluids Barriers CNS"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1093\/cercor\/bhv078","article-title":"Defects During Mecp2 Null Embryonic Cortex Development Precede the Onset of Overt Neurological Symptoms","volume":"26","author":"Bedogni","year":"2015","journal-title":"Cereb. Cortex"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.autrev.2016.01.011","article-title":"Rett syndrome: An autoimmune disease?","volume":"15","author":"Leoncini","year":"2016","journal-title":"Autoimmun. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1093\/brain\/awq314","article-title":"SOD1 targeted to the mitochondrial intermembrane space prevents motor neuropathy in the Sod1 knockout mouse","volume":"134","author":"Fischer","year":"2010","journal-title":"Brain"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1038\/ejhg.2015.21","article-title":"CACNA1A haploinsufficiency causes cognitive impairment, autism and epileptic encephalopathy with mild cerebellar symptoms","volume":"23","author":"Damaj","year":"2015","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1177\/0883073818754987","article-title":"An Atypical Rett Syndrome Phenotype Due to a Novel Missense Mutation in CACNA1A","volume":"33","author":"Epperson","year":"2018","journal-title":"J. Child Neurol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0896-6273(02)00942-X","article-title":"Mechanism of TrkB-mediated hippocampal long-term potentiation","volume":"36","author":"Minichiello","year":"2002","journal-title":"Neuron"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"561","DOI":"10.3389\/fgene.2020.00561","article-title":"Candidate Genes Associated with Neurological Findings in a Patient with Trisomy 4p16.3 and Monosomy 5p15.2","volume":"11","author":"Poswar","year":"2020","journal-title":"Front. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Antona, V., Scalia, F., Giorgio, E., Radio, F., Brusco, A., Oliveri, M., Corsello, G., Celso, F.L., Vadal\u00e0, M., and De Macario, E.C. (2020). A Novel CCT5 Missense Variant Associated with Early Onset Motor Neuropathy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207631"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1093\/oxfordjournals.jbchem.a002955","article-title":"Analysis of tyrosine phosphorylation-dependent protein-protein interactions in TrkB-mediated intracellular signaling using modified yeast two-hybrid system","volume":"130","author":"Yamada","year":"2001","journal-title":"J. Biochem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3671","DOI":"10.1523\/JNEUROSCI.3735-16.2017","article-title":"CREB Signaling Is Involved in Rett Syndrome Pathogenesis","volume":"37","author":"Bu","year":"2017","journal-title":"J. Neurosci. Off. J. Soc.Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1186\/s13041-020-00707-0","article-title":"Integrin \u03b23 organizes dendritic complexity of cerebral cortical pyramidal neurons along a tangential gradient","volume":"13","author":"Swinehart","year":"2020","journal-title":"Mol. Brain"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"8467","DOI":"10.1073\/pnas.0308455101","article-title":"NMDA receptor hypofunction produces concomitant firing rate potentiation and burst activity reduction in the prefrontal cortex","volume":"101","author":"Jackson","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"13860","DOI":"10.1523\/JNEUROSCI.2159-12.2012","article-title":"Brain Activity Mapping in Mecp2 Mutant Mice Reveals Functional Deficits in Forebrain Circuits, Including Key Nodes in the Default Mode Network, that are Reversed with Ketamine Treatment","volume":"32","author":"Kron","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.resp.2011.02.002","article-title":"The benzodiazepine Midazolam mitigates the breathing defects of Mecp2-deficient mice","volume":"177","author":"Voituron","year":"2011","journal-title":"Respir. Physiol. Neurobiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1242\/jcs.068759","article-title":"TOX3 is a neuronal survival factor that induces transcription depending on the presence of CITED1 or phosphorylated CREB in the transcriptionally active complex","volume":"124","author":"Dittmer","year":"2011","journal-title":"J. Cell Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1111\/j.1471-4159.2009.06160.x","article-title":"Heme oxygenase-1 and neurodegeneration: Expanding frontiers of engagement","volume":"110","author":"Schipper","year":"2009","journal-title":"J. Neurochem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1007\/s13311-015-0353-y","article-title":"Rett Syndrome: Reaching for Clinical Trials","volume":"12","author":"Pati","year":"2015","journal-title":"Neurotherapeutics"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.pediatrneurol.2016.05.010","article-title":"Pharmacologic Treatment of Rett Syndrome with Glatiramer Acetate","volume":"61","author":"Djukic","year":"2016","journal-title":"Pediatr. Neurol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13023-020-01655-7","article-title":"Fingolimod in children with Rett syndrome: The FINGORETT study","volume":"16","author":"Naegelin","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.pediatrneurol.2016.11.006","article-title":"A Potential Life-Threatening Reaction to Glatiramer Acetate in Rett Syndrome","volume":"68","author":"Nissenkorn","year":"2017","journal-title":"Pediatr. Neurol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"R29","DOI":"10.1186\/gb-2014-15-2-r29","article-title":"Voom: Precision weights unlock linear model analysis tools for RNA-seq read counts","volume":"15","author":"Law","year":"2014","journal-title":"Genome Biol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Langfelder, P., and Horvath, S. (2008). WGCNA: An R package for weighted correlation network analysis. BMC Bioinform., 9.","DOI":"10.1186\/1471-2105-9-559"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: Kyoto encyclopedia of genes and genomes","volume":"28","author":"Kanehisa","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"D590","DOI":"10.1093\/nar\/gky962","article-title":"New approach for understanding genome variations in KEGG","volume":"47","author":"Kanehisa","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"D605","DOI":"10.1093\/nar\/gkaa1074","article-title":"The STRING database in 2021: Customizable protein-protein networks, and functional characterization of user-uploaded gene\/measurement sets","volume":"49","author":"Szklarczyk","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1007\/s10354-016-0488-4","article-title":"New insights in Rett syndrome using pathway analysis for transcriptomics data","volume":"166","author":"Ehrhart","year":"2016","journal-title":"Wien. Med. Wochenschr."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11125\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:37:08Z","timestamp":1760143028000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11125"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,22]]},"references-count":69,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["ijms231911125"],"URL":"https:\/\/doi.org\/10.3390\/ijms231911125","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints202207.0030.v1","asserted-by":"object"}]},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,22]]}}}