{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T16:01:18Z","timestamp":1761580878113},"reference-count":24,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2011,5,23]],"date-time":"2011-05-23T00:00:00Z","timestamp":1306108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2012,6]]},"abstract":"<jats:p>Chabchoub E, Willekens D, Vermeesch JR, Fryns J\u2010P. Holoprosencephaly and <jats:italic>ZIC2<\/jats:italic> microdeletions: novel clinical and epidemiological specificities delineated.<\/jats:p><jats:p>Holoprosencephaly (HPE), the most common malformation of the human brain results from abnormal cleavage of the forebrain during the early embryonic developmental stages. The spectrum of malformations in HPE is wide, ranging from the classical cyclopia\/proboscis to fairly asymptomatic forms [i.e. a single maxillary central incisor (SMCI)]. HPE may be caused by environmental or genetic factors. <jats:italic>ZIC2<\/jats:italic> (13q32) was the second gene identified in which mutations cause HPE and recently a specific phenotype was ascribed to <jats:italic>ZIC2<\/jats:italic>\u2010mutation HPE.<\/jats:p><jats:p>Earlier, we reported a boy presenting HPE and deafness. Cytogenetic analyses were normal. Using array\u2010comparative genomic hybridization (aCGH), we found a <jats:italic>de novo<\/jats:italic> 129 kb del(13)(q32) encompassing <jats:italic>ZIC2<\/jats:italic> and <jats:italic>ZIC5<\/jats:italic>. There is no evidence for the involvement of <jats:italic>ZIC5<\/jats:italic> in human diseases. We reviewed the literature for <jats:italic>ZIC2<\/jats:italic>\u2010<jats:italic>ZIC5<\/jats:italic> deletions and their involvement in neural tube defects (NTDs).<\/jats:p><jats:p>Interestingly, we found evidence for a specific facial phenotype for <jats:italic>ZIC2<\/jats:italic> gene deletion patients distinct from those with point mutations. In addition, based on the clinical data together with pathology, imaging and functional studies, we suggest an outline for a model explaining the genetic heterogeneity of <jats:italic>ZIC2<\/jats:italic>\u2010<jats:italic>ZIC5<\/jats:italic>\u2010associated NTDs and propose further studies for validation.<\/jats:p>","DOI":"10.1111\/j.1399-0004.2011.01684.x","type":"journal-article","created":{"date-parts":[[2011,4,16]],"date-time":"2011-04-16T03:01:24Z","timestamp":1302922884000},"page":"584-589","source":"Crossref","is-referenced-by-count":4,"title":["Holoprosencephaly and <i>ZIC2<\/i> microdeletions: novel clinical and epidemiological specificities delineated"],"prefix":"10.1111","volume":"81","author":[{"given":"E","family":"Chabchoub","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D","family":"Willekens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JR","family":"Vermeesch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u2010P","family":"Fryns","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,5,23]]},"reference":[{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/MOP.0b013e32833f56d5"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-2-8"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/2484"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2005.00418.x"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.073049"},{"key":"e_1_2_8_7_2","first-page":"399","article-title":"On the association profound nerve deafness, semilobar holoprosencephaly, and minor midline developmental anomalies.","volume":"10","author":"Vantrappen G","year":"1999","journal-title":"Genet Couns"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2006.043059"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32814"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33550"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2008.10.002"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s003810100471"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00262269"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10659"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.043471"},{"key":"e_1_2_8_16_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02756"},{"key":"e_1_2_8_17_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.037820"},{"key":"e_1_2_8_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.4.1618"},{"key":"e_1_2_8_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2004.02.017"},{"key":"e_1_2_8_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1420"},{"key":"e_1_2_8_21_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02239"},{"key":"e_1_2_8_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.230"},{"key":"e_1_2_8_23_2","doi-asserted-by":"publisher","DOI":"10.1159\/000302285"},{"key":"e_1_2_8_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2010.70"},{"key":"e_1_2_8_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.30240"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1399-0004.2011.01684.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1399-0004.2011.01684.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T03:28:17Z","timestamp":1698722897000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1399-0004.2011.01684.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,5,23]]},"references-count":24,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2012,6]]}},"alternative-id":["10.1111\/j.1399-0004.2011.01684.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1399-0004.2011.01684.x","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,5,23]]}}}