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MOWS is characterized by intellectual disability, epilepsy, typical facial phenotype and other anomalies, such as short stature, Hirschsprung disease, brain and heart defects. Despite some recognizable features, MOWS rarity and phenotypic variability may complicate its diagnosis, particularly in the neonatal period. In order to define a novel diagnostic biomarker for MOWS, we determined the genome-wide DNA methylation profile of DNA samples from 29 individuals with confirmed clinical and molecular diagnosis. Through multidimensional scaling and hierarchical clustering analysis, we identified and validated a DNA methylation signature involving 296 differentially methylated probes as part of the broader MOWS DNA methylation profile. The prevalence of hypomethylated CpG sites agrees with the main role of ZEB2 as a transcriptional repressor, while differential methylation within the <jats:italic>ZEB2<\/jats:italic> locus supports the previously proposed autoregulation ability. Correlation studies compared the MOWS cohort with 56 previously described DNA methylation profiles of other neurodevelopmental disorders, further validating the specificity of this biomarker. In conclusion, MOWS DNA methylation signature is highly sensitive and reproducible, providing a useful tool to facilitate diagnosis.<\/jats:p>","DOI":"10.1038\/s41431-024-01548-4","type":"journal-article","created":{"date-parts":[[2024,2,13]],"date-time":"2024-02-13T08:02:05Z","timestamp":1707811325000},"page":"619-629","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Identification of the DNA methylation signature of Mowat-Wilson syndrome"],"prefix":"10.1038","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5033-7854","authenticated-orcid":false,"given":"Stefano Giuseppe","family":"Caraffi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7800-8665","authenticated-orcid":false,"given":"Liselot","family":"van der Laan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7871-8982","authenticated-orcid":false,"given":"Kathleen","family":"Rooney","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Slavica","family":"Trajkova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Zuntini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raissa","family":"Relator","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sadegheh","family":"Haghshenas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael A.","family":"Levy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Baldo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0849-2225","authenticated-orcid":false,"given":"Giorgia","family":"Mandrile","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolyn","family":"Lauzon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duccio Maria","family":"Cordelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan","family":"Ivanovski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Fetta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9702-3994","authenticated-orcid":false,"given":"Elena","family":"Sukarova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8318-7231","authenticated-orcid":false,"given":"Alfredo","family":"Brusco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7630-8365","authenticated-orcid":false,"given":"Lisa","family":"Pavinato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0409-9832","authenticated-orcid":false,"given":"Verdiana","family":"Pullano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4871-9519","authenticated-orcid":false,"given":"Marcella","family":"Zollino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haley","family":"McConkey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7736-9672","authenticated-orcid":false,"given":"Marco","family":"Tartaglia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni Battista","family":"Ferrero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6363-0016","authenticated-orcid":false,"given":"Bekim","family":"Sadikovic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7684-3982","authenticated-orcid":false,"given":"Livia","family":"Garavelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,2,13]]},"reference":[{"key":"1548_CR1","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1136\/jmg.35.8.617","volume":"35","author":"DR Mowat","year":"1998","unstructured":"Mowat DR, Croaker GD, Cass DT, Kerr BA, Chaitow J, Ad\u00e8s LC, et al. 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The study was approved by the Research Ethics Committee of Area Vasta Emilia Nord (CE-AVEN 06\/09\/2022, 529\/2022\/TESS\/AUSLRE, protocol no. 2022\/0112043) and by the competent local institutional review boards. Written informed consent to publish clinical and genetic information was obtained from the parents\/legal guardians of the individuals whose samples were included in this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}