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Supervised machine-learning classification demonstrated high sensitivity and specificity, with reproducibility confirmed by leave-one-out cross-validation, as well as correctly classifying a validation case with a pathogenic\n                    <jats:italic>ZNF462<\/jats:italic>\n                    variant. Comparative analysis revealed partial overlap of genome-wide DNA methylation changes between the WSKA episignature and other neurodevelopmental disorders involving chromatin regulators. Functional annotation of differentially methylated probes and regions demonstrated enrichment for pathways related to neurodevelopment, neuron function and cell adhesion. These findings define and validate a distinct DNAm episignature for WSKA, providing a valuable diagnostic biomarker to support variant classification and offering insight into the epigenomic consequences of ZNF462 haploinsufficiency.\n                  <\/jats:p>","DOI":"10.1007\/s00439-026-02846-1","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T06:29:03Z","timestamp":1784528943000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Discovery of a DNA methylation episignature for Weiss-Kruszka syndrome"],"prefix":"10.1007","volume":"145","author":[{"given":"Haley","family":"McConkey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liselot","family":"van der Laan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sourav","family":"Ghosh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lotte","family":"Kleinendorst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Levy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Rzasa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna M.","family":"van Hagen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quinten","family":"Waisfisz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi L.","family":"Schulz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corina","family":"Heller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Huhn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolin D.","family":"Obermaier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konrad","family":"Platzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rami Abou","family":"Jamra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikos","family":"Marinakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danai","family":"Veltra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantina","family":"Kosma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christalena","family":"Sofocleous","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Henneman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bekim","family":"Sadikovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mieke M.","family":"van Haelst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"issue":"11","key":"2846_CR1","doi-asserted-by":"publisher","first-page":"1517","DOI":"10.1002\/humu.23626","volume":"39","author":"AN Abou Tayoun","year":"2018","unstructured":"Abou Tayoun AN, Pesaran T, DiStefano MT, Oza A, Rehm HL, Biesecker LG et al (2018) Recommendations for interpreting the loss of function PVS1 ACMG\/AMP variant criterion. 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