{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T10:27:52Z","timestamp":1783765672276,"version":"3.55.0"},"reference-count":88,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,21]],"date-time":"2023-05-21T00:00:00Z","timestamp":1684627200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"TGen\u2019s Center for Rare Childhood Disorders (C4RCD)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Mutations of the X-linked gene encoding methyl-CpG-binding protein 2 (MECP2) cause classical forms of Rett syndrome (RTT) in girls. A subset of patients who are recognized to have an overlapping neurological phenotype with RTT but are lacking a mutation in a gene that causes classical or atypical RTT can be described as having a \u2018Rett-syndrome-like phenotype (RTT-L). Here, we report eight patients from our cohort diagnosed as having RTT-L who carry mutations in genes unrelated to RTT. We annotated the list of genes associated with RTT-L from our patient cohort, considered them in the light of peer-reviewed articles on the genetics of RTT-L, and constructed an integrated protein\u2013protein interaction network (PPIN) consisting of 2871 interactions connecting 2192 neighboring proteins among RTT- and RTT-L-associated genes. Functional enrichment analysis of RTT and RTT-L genes identified a number of intuitive biological processes. We also identified transcription factors (TFs) whose binding sites are common across the set of RTT and RTT-L genes and appear as important regulatory motifs for them. Investigation of the most significant over-represented pathway analysis suggests that HDAC1 and CHD4 likely play a central role in the interactome between RTT and RTT-L genes.<\/jats:p>","DOI":"10.3390\/cells12101437","type":"journal-article","created":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T01:31:46Z","timestamp":1684719106000},"page":"1437","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Genetic and Protein Network Underlying the Convergence of Rett-Syndrome-like (RTT-L) Phenotype in Neurodevelopmental Disorders"],"prefix":"10.3390","volume":"12","author":[{"given":"Eric","family":"Frankel","sequence":"first","affiliation":[{"name":"Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8296-0034","authenticated-orcid":false,"given":"Avijit","family":"Podder","sequence":"additional","affiliation":[{"name":"Quantitative Medicine Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Sharifi","sequence":"additional","affiliation":[{"name":"Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roshan","family":"Pillai","sequence":"additional","affiliation":[{"name":"Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Newell","family":"Belnap","sequence":"additional","affiliation":[{"name":"Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA"},{"name":"Center for Rare Childhood Disorders (C4RCD), Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keri","family":"Ramsey","sequence":"additional","affiliation":[{"name":"Center for Rare Childhood Disorders (C4RCD), Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julius","family":"Dodson","sequence":"additional","affiliation":[{"name":"Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pooja","family":"Venugopal","sequence":"additional","affiliation":[{"name":"Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0417-3406","authenticated-orcid":false,"given":"Molly","family":"Brzezinski","sequence":"additional","affiliation":[{"name":"Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorida","family":"Llaci","sequence":"additional","affiliation":[{"name":"Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA"},{"name":"Quantitative Medicine Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany","family":"Gerald","sequence":"additional","affiliation":[{"name":"Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle","family":"Mills","sequence":"additional","affiliation":[{"name":"Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meredith","family":"Sanchez-Castillo","sequence":"additional","affiliation":[{"name":"Center for Rare Childhood Disorders (C4RCD), Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris D.","family":"Balak","sequence":"additional","affiliation":[{"name":"Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szabolcs","family":"Szelinger","sequence":"additional","affiliation":[{"name":"Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3020-6005","authenticated-orcid":false,"given":"Wayne M.","family":"Jepsen","sequence":"additional","affiliation":[{"name":"Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley L.","family":"Siniard","sequence":"additional","affiliation":[{"name":"Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Richholt","sequence":"additional","affiliation":[{"name":"Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Naymik","sequence":"additional","affiliation":[{"name":"Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7310-6082","authenticated-orcid":false,"given":"Isabelle","family":"Schrauwen","sequence":"additional","affiliation":[{"name":"Center for Statistical Genetics, Department of Neurology, Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Craig","sequence":"additional","affiliation":[{"name":"Department of Translational Genomics, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4024-3368","authenticated-orcid":false,"given":"Ignazio S.","family":"Piras","sequence":"additional","affiliation":[{"name":"Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7390-9918","authenticated-orcid":false,"given":"Matthew J.","family":"Huentelman","sequence":"additional","affiliation":[{"name":"Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA"},{"name":"Quantitative Medicine Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0920-5013","authenticated-orcid":false,"given":"Nicholas J.","family":"Schork","sequence":"additional","affiliation":[{"name":"Quantitative Medicine Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA"},{"name":"City of Hope National Medical Center, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinodh","family":"Narayanan","sequence":"additional","affiliation":[{"name":"Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA"},{"name":"Center for Rare Childhood Disorders (C4RCD), Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2151-9162","authenticated-orcid":false,"given":"Sampathkumar","family":"Rangasamy","sequence":"additional","affiliation":[{"name":"Neurogenomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA"},{"name":"Center for Rare Childhood Disorders (C4RCD), Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,21]]},"reference":[{"key":"ref_1","first-page":"723","article-title":"On a unusual brain atrophy syndrome in hyperammonemia in childhood","volume":"116","author":"Rett","year":"1966","journal-title":"Wien. 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