{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T12:19:17Z","timestamp":1780057157079,"version":"3.54.0"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,3,24]],"date-time":"2018-03-24T00:00:00Z","timestamp":1521849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Patients with pathogenic variants in <jats:italic>ZBTB18<\/jats:italic> present with Intellectual Disability (ID) with frequent co\u2010occurrence of corpus callosum (CC) anomalies, hypotonia, microcephaly, growth problems and variable facial dysmorphologies. These features illustrate a key role for <jats:italic>ZBTB18<\/jats:italic> in brain development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with a pathogenic variant in <jats:italic>ZBTB18<\/jats:italic> were detected by diagnostic whole exome sequencing (WES) performed in our center. We reviewed the literature and used GeneMatcher to include other cases. YASARA and WHAT IF were used to provide insight into the structural effect of missense variants located in the C2H2 zinc finger domains of the ZBTB18 protein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We give a complete overview of pathogenic variants in <jats:italic>ZBTB18<\/jats:italic> detected to date, showing inconsistent presence of clinical features, including CC anomalies. We present four new cases with a de novo pathogenic variant in the <jats:italic>ZBTB18<\/jats:italic> gene, including the fourth case in which a de novo p.Arg464His variant was found.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Homology modeling of protein structure points to a variable degree of impaired DNA binding caused by missense variants in these domains probably leading to Loss of Function (LoF). Putative partial LoF may present with a less distinctive phenotype than complete LoF, as seen in truncating variants, which presents with an extensive variability in the phenotypic spectrum. Our data do not support a clear genotype to phenotype correlation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.387","type":"journal-article","created":{"date-parts":[[2018,3,24]],"date-time":"2018-03-24T23:50:14Z","timestamp":1521935414000},"page":"393-400","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Toward clinical and molecular understanding of pathogenic variants in the <i>ZBTB18<\/i> gene"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9829-9220","authenticated-orcid":false,"given":"Vyne","family":"van der Schoot","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics Maastricht University Medical Centre Maastricht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"de Munnik","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud University Medical Centre Nijmegen Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanka","family":"Venselaar","sequence":"additional","affiliation":[{"name":"Centre for Molecular and Biomolecular Informatics (CMBI) Radboud University Medical Centre Nijmegen Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariet","family":"Elting","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Vrije Universiteit Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazia M. S.","family":"Mancini","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Erasmus MC University Medical Centre Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conny M. A.","family":"Ravenswaaij\u2010Arts","sequence":"additional","affiliation":[{"name":"University of Groningen University Medical Centre Groningen Department of Genetics Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britt\u2010Marie","family":"Anderlid","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Karolinska Universitetssjukhuset Solna Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han G.","family":"Brunner","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Maastricht University Medical Centre Maastricht the Netherlands"},{"name":"Department of Human Genetics Radboud University Medical Centre Nijmegen Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8769-3150","authenticated-orcid":false,"given":"Servi J. 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