{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:08:00Z","timestamp":1790370480209,"version":"4.1.0"},"reference-count":54,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T00:00:00Z","timestamp":1709164800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Mowat\u2013Wilson Syndrome Foundation","award":["KU Endowment 41149"],"award-info":[{"award-number":["KU Endowment 41149"]}]},{"name":"Mowat\u2013Wilson Syndrome Foundation","award":["U54 HD061222"],"award-info":[{"award-number":["U54 HD061222"]}]},{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development (NICHD)","doi-asserted-by":"publisher","award":["KU Endowment 41149"],"award-info":[{"award-number":["KU Endowment 41149"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development (NICHD)","doi-asserted-by":"publisher","award":["U54 HD061222"],"award-info":[{"award-number":["U54 HD061222"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mowat\u2013Wilson syndrome (MWS) is a rare genetic neurodevelopmental congenital disorder associated with various defects of the zinc finger E-box binding homeobox 2 (ZEB2) gene. The ZEB2 gene is autosomal dominant and encodes six protein domains including the SMAD-binding protein, which functions as a transcriptional corepressor involved in the conversion of neuroepithelial cells in early brain development and as a mediator of trophoblast differentiation. This review summarizes reported ZEB2 gene variants, their types, and frequencies among the 10 exons of ZEB2. Additionally, we summarized their corresponding encoded protein defects including the most common variant, c.2083 C&gt;T in exon 8, which directly impacts the homeodomain (HD) protein domain. This single defect was found in 11% of the 298 reported patients with MWS. This review demonstrates that exon 8 encodes at least three of the six protein domains and accounts for 66% (198\/298) of the variants identified. More than 90% of the defects were due to nonsense or frameshift changes. We show examples of protein modeling changes that occurred as a result of ZEB2 gene defects. We also report a novel pathogenic variant in exon 8 in a 5-year-old female proband with MWS. This review further explores other genes predicted to be interacting with the ZEB2 gene and their predicted gene\u2013gene molecular interactions with protein binding effects on embryonic multi-system development such as craniofacial, spine, brain, kidney, cardiovascular, and hematopoiesis.<\/jats:p>","DOI":"10.3390\/ijms25052838","type":"journal-article","created":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T08:13:44Z","timestamp":1709194424000},"page":"2838","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Mowat\u2013Wilson Syndrome: Case Report and Review of ZEB2 Gene Variant Types, Protein Defects and Molecular Interactions"],"prefix":"10.3390","volume":"25","author":[{"given":"Caroline","family":"St. Peter","sequence":"first","affiliation":[{"name":"Departments of Psychiatry & Behavioral Sciences and Pediatrics, University of Kansas Medical Center, 3901 Rainbow Blvd. MS 4015, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waheeda A.","family":"Hossain","sequence":"additional","affiliation":[{"name":"Departments of Psychiatry & Behavioral Sciences and Pediatrics, University of Kansas Medical Center, 3901 Rainbow Blvd. MS 4015, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3215-4472","authenticated-orcid":false,"given":"Scott","family":"Lovell","sequence":"additional","affiliation":[{"name":"Protein Structure Laboratory, University of Kansas, Lawrence, KS 66047, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1797-1925","authenticated-orcid":false,"given":"Syed K.","family":"Rafi","sequence":"additional","affiliation":[{"name":"Departments of Psychiatry & Behavioral Sciences and Pediatrics, University of Kansas Medical Center, 3901 Rainbow Blvd. MS 4015, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2911-0524","authenticated-orcid":false,"given":"Merlin G.","family":"Butler","sequence":"additional","affiliation":[{"name":"Departments of Psychiatry & Behavioral Sciences and Pediatrics, University of Kansas Medical Center, 3901 Rainbow Blvd. MS 4015, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/d41573-019-00180-y","article-title":"How many rare diseases are there?","volume":"19","author":"Haendel","year":"2020","journal-title":"Nat. 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