{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:57:45Z","timestamp":1792623465150,"version":"4.5.0"},"reference-count":47,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T00:00:00Z","timestamp":1631664000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Neil and Norma Hill Foundation","award":["CON204635"],"award-info":[{"award-number":["CON204635"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Rett Syndrome (RTT) is an X linked neurodevelopmental disorder caused by mutations in the methyl-CpG-binding protein 2 (MECP2) gene, resulting in severe cognitive and physical disabilities. Despite an apparent normal prenatal and postnatal development period, symptoms usually present around 6 to 18 months of age. Little is known about the consequences of MeCP2 deficiency at a molecular and cellular level before the onset of symptoms in neural cells, and subtle changes at this highly sensitive developmental stage may begin earlier than symptomatic manifestation. Recent transcriptomic studies of patient induced pluripotent stem cells (iPSC)-differentiated neurons and brain organoids harbouring pathogenic mutations in MECP2, have unravelled new insights into the cellular and molecular changes caused by these mutations. Here we interrogated transcriptomic modifications in RTT patients using publicly available RNA-sequencing datasets of patient iPSCs harbouring pathogenic mutations and healthy control iPSCs by Weighted Gene Correlation Network Analysis (WGCNA). Preservation analysis identified core gene pathways involved in translation, ribosomal function, and ubiquitination perturbed in some MECP2 mutant iPSC lines. Furthermore, differential gene expression of the parental fibroblasts and iPSC-derived neurons revealed alterations in genes in the ubiquitination pathway and neurotransmission in fibroblasts and differentiated neurons respectively. These findings might suggest that global translational dysregulation and proteasome ubiquitin function in Rett syndrome begins in progenitor cells prior to lineage commitment and differentiation into neural cells.<\/jats:p>","DOI":"10.3390\/ijms22189954","type":"journal-article","created":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T04:50:28Z","timestamp":1631681428000},"page":"9954","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["WGCNA Identifies Translational and Proteasome-Ubiquitin Dysfunction in Rett Syndrome"],"prefix":"10.3390","volume":"22","author":[{"given":"Florencia","family":"Haase","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Health, School of Medical Science, The University of Sydney, Camperdown, NSW 2050, 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":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian S.","family":"Gloss","sequence":"additional","affiliation":[{"name":"Westmead Research Hub, Westmead Institute for Medical Research, Westmead, NSW 2145, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick P. L.","family":"Tam","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health, School of Medical Science, The University of Sydney, Camperdown, NSW 2050, Australia"},{"name":"Embryology Research Unit, Children\u2019s Medical Research Institute, The University of Sydney, Sydney, NSW 2145, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1808-0646","authenticated-orcid":false,"given":"Wendy A.","family":"Gold","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health, School of Medical Science, The University of Sydney, Camperdown, NSW 2050, 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":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1136\/jmg.2004.027730","article-title":"Rett syndrome: Clinical review and genetic update","volume":"42","author":"Weaving","year":"2005","journal-title":"J. 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