{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T22:23:02Z","timestamp":1780957382346,"version":"3.54.1"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,3,27]],"date-time":"2017-03-27T00:00:00Z","timestamp":1490572800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Charit\u00e9-Universit\u00e4tsmedizin Berlin and the Berlin Institute of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:sec><jats:label\/><jats:p><jats:italic>ZBTB18<\/jats:italic> has been proposed as candidate gene for microcephaly and abnormalities of the corpus callosum based on overlapping microdeletions of 1q43q44. More recently, de novo mutations of <jats:italic>ZBTB18<\/jats:italic> have been identified in patients with syndromic and non\u2010syndromic intellectual disability. Heterozygous microdeletions of 15q13.3 encompassing the candidate gene <jats:italic>CHRNA7<\/jats:italic> are associated with developmental delay or intellectual disability with speech problems, hypotonia, and seizures. They are characterized by significant variability and reduced penetrance. We report on a patient with a de novo <jats:italic>ZBTB18<\/jats:italic> nonsense mutation and a de novo 15q13.3 microdeletion, both in a heterozygous state, identified by next generation sequencing and array\u2010CGH. The 6\u2010year\u2010old girl showed global developmental delay, absent speech, therapy\u2010refractory seizures, ataxia, muscular hypotonia, and discrete facial dysmorphisms. Almost all of these features have been reported for both genetic aberrations, but the severity could hardly been explained by the microdeletion 15q13.3 alone. We assume an additive effect of haploinsufficiency of <jats:italic>ZBTB18<\/jats:italic> and <jats:italic>CHRNA7<\/jats:italic> in our patient. Assembling the features of our patient and the published patients, we noted that only one of them showed mild anomalies of the corpus callosum. Moreover, we hypothesize that nonsense mutations of <jats:italic>ZBTB18<\/jats:italic> are associated with a more severe phenotype than missense mutations. This report indicates that haploinsufficiency of additional genes beside <jats:italic>ZBTB18<\/jats:italic> causes the high frequency of corpus callosum anomalies in patients with microdeletions of 1q43q44 and underlines the importance of an NGS\u2010based molecular diagnostic in complex phenotypes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38145","type":"journal-article","created":{"date-parts":[[2017,3,27]],"date-time":"2017-03-27T10:14:04Z","timestamp":1490609644000},"page":"1251-1256","source":"Crossref","is-referenced-by-count":8,"title":["A de novo nonsense mutation in <i>ZBTB18<\/i> plus a de novo 15q13.3 microdeletion in a 6\u2010year\u2010old female"],"prefix":"10.1002","volume":"173","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1449-9909","authenticated-orcid":false,"given":"Nadja","family":"Ehmke","sequence":"first","affiliation":[{"name":"Institute of Medical Genetics and Human Genetics Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin Berlin 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