{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:39:33Z","timestamp":1791499173698,"version":"4.3.4"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,10,10]],"date-time":"2016-10-10T00:00:00Z","timestamp":1476057600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000893","name":"Simons Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000893","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:p>Identification of rare genetic variants in patients with intellectual disability (<jats:styled-content style=\"fixed-case\">ID<\/jats:styled-content>) has been greatly accelerated by advances in next generation sequencing technologies. However, due to small numbers of patients, the complete phenotypic spectrum associated with pathogenic variants in single genes is still emerging. Among these genes is <jats:italic><jats:styled-content style=\"fixed-case\">ZBTB18<\/jats:styled-content><\/jats:italic> (<jats:italic><jats:styled-content style=\"fixed-case\">ZNF238<\/jats:styled-content><\/jats:italic>), which is deleted in patients with 1q43q44 microdeletions who typically present with <jats:styled-content style=\"fixed-case\">ID<\/jats:styled-content>, microcephaly, corpus callosum (<jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>) abnormalities, and seizures. Here we provide additional evidence for haploinsufficiency or dysfunction of the <jats:italic><jats:styled-content style=\"fixed-case\">ZBTB18<\/jats:styled-content><\/jats:italic> gene as the cause of <jats:styled-content style=\"fixed-case\">ID<\/jats:styled-content> in five unrelated patients with variable syndromic features who underwent whole exome sequencing revealing separate <jats:italic>de novo<\/jats:italic> pathogenic or likely pathogenic variants in <jats:italic><jats:styled-content style=\"fixed-case\">ZBTB18<\/jats:styled-content><\/jats:italic> (two missense alterations and three truncating alterations). The neuroimaging findings in our cohort (<jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content> hypoplasia seen in 4\/4 of our patients who underwent <jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content>) lend further support for <jats:italic><jats:styled-content style=\"fixed-case\">ZBTB18<\/jats:styled-content><\/jats:italic> as a critical gene for <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content> abnormalities. A similar phenotype of microcephaly, <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content> agenesis, and cerebellar vermis hypoplasia has been reported in mice with central nervous system\u2010specific knockout of <jats:italic>Zbtb18<\/jats:italic>. Our five patients, in addition to the previously described cases of <jats:italic>de novo <jats:styled-content style=\"fixed-case\">ZBTB18<\/jats:styled-content><\/jats:italic> variants, add to knowledge about the phenotypic spectrum associated with <jats:italic><jats:styled-content style=\"fixed-case\">ZBTB18<\/jats:styled-content><\/jats:italic> haploinsufficiency\/dysfunction.<\/jats:p>","DOI":"10.1111\/cge.12861","type":"journal-article","created":{"date-parts":[[2016,9,6]],"date-time":"2016-09-06T13:47:01Z","timestamp":1473169621000},"page":"697-707","source":"Crossref","is-referenced-by-count":40,"title":["Further evidence that <i>de novo<\/i> missense and truncating variants in <i><scp>ZBTB18<\/scp><\/i> cause intellectual disability with variable features"],"prefix":"10.1111","volume":"91","author":[{"given":"J.S.","family":"Cohen","sequence":"first","affiliation":[{"name":"Division of Neurogenetics Hugo W. Moser Research Institute, Kennedy Krieger Institute  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Division of Neurogenetics Hugo W. Moser Research Institute, Kennedy Krieger Institute  Baltimore MD USA"},{"name":"Department of Neurology The Johns Hopkins Hospital  Baltimore MD USA"},{"name":"Department of Pediatrics The Johns Hopkins Hospital  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.D.","family":"Farwell Hagman","sequence":"additional","affiliation":[{"name":"Division of Clinical Genomics Ambry Genetics  Aliso Viejo CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.N.","family":"Shinde","sequence":"additional","affiliation":[{"name":"Division of Clinical Genomics Ambry Genetics  Aliso Viejo CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Huether","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics Ambry Genetics  Aliso Viejo CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Darcy","sequence":"additional","affiliation":[{"name":"Silicon Valley Genetics Center, Santa Clara Valley Medical Center  San Jose CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Wallerstein","sequence":"additional","affiliation":[{"name":"Hawaii Community Genetics Kapiolani Medical Center for Women and Children  Honolulu HI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Houge","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics and Molecular Medicine Haukeland University Hospital  Bergen Norway"},{"name":"Department of Medical Genetics St. Olav Hospital  Trondheim Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Berland","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics and Molecular Medicine Haukeland University Hospital  Bergen Norway"},{"name":"Department of Medical Genetics St. Olav Hospital  Trondheim Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.G.","family":"Monaghan","sequence":"additional","affiliation":[{"name":"GeneDx  Gaithersburg MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Poretti","sequence":"additional","affiliation":[{"name":"Section of Pediatric Neuroradiology, Division of Pediatric Radiology, Russell H. 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