{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T06:11:40Z","timestamp":1761718300342},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,2,12]],"date-time":"2014-02-12T00:00:00Z","timestamp":1392163200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Holoprosencephaly (HPE) is a spectrum of midline malformations of the prosencephalon generally reflected in a continuum of midline facial anomalies. Patients with mutation in the <jats:italic>ZIC2<\/jats:italic> gene usually present a normal or mildly dysmorphic face associated with a severe brain malformation. Here we present a rare unilateral nasal cleft (Tessier cleft n. 1) with holoprosencephaly in a patient with a <jats:italic>ZIC2<\/jats:italic> mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>CASE<\/jats:title><jats:p>The male newborn presented with alobar HPE, microcephaly, ocular hypertelorism, upslanting palpebral fissures, a bulky nose with a left paramedian alar cleft. Mutational screening for HPE genes revealed the occurrence of a frameshift mutation in the <jats:italic>ZIC2<\/jats:italic> gene. The mutation was inherited from the father who presented only mild ocular hypotelorism but had an affected child with HPE from his first marriage.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>The occurrence of oral clefts is common in patients with HPE, but unusual in patients with mutation in the <jats:italic>ZIC2<\/jats:italic> gene. To our knowledge, clefts of the nasal alae have been reported only once or twice in patients with <jats:italic>ZIC2<\/jats:italic> mutations. In documented patients from the literature, only 2% of individuals with described pathogenic mutations in the <jats:italic>ZIC2<\/jats:italic> gene (3\/171) presented facial clefts, one of them a nasal cleft, while common oral clefts were observed in 27% of individuals (7\/26) described with nonpathogenic <jats:italic>ZIC2<\/jats:italic> mutations or presenting a concomitant mutation in another HPE gene. When compared with the general population, nasal clefts are common in <jats:italic>ZIC2<\/jats:italic> mutations and these mutations must be searched for in undiagnosed cases. Birth Defects Research (Part A) 100:300\u2013306, 2014. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.23216","type":"journal-article","created":{"date-parts":[[2014,2,12]],"date-time":"2014-02-12T12:31:04Z","timestamp":1392208264000},"page":"300-306","source":"Crossref","is-referenced-by-count":8,"title":["Rare nasal cleft in a patient with holoprosencephaly due to a mutation in the <i>ZIC2<\/i> gene"],"prefix":"10.1002","volume":"100","author":[{"given":"Clarice Pagani","family":"Savastano","sequence":"first","affiliation":[{"name":"Estudo Colaborativo Latino Americano de Malforma\u00e7\u00f5es Cong\u00eanitas (ECLAMC) Departamento de Gen\u00e9tica Universidade Federal do Rio de Janeiro  Brazil"},{"name":"INAGEMP \u2013 Instituto Nacional de Gen\u00e9tica M\u00e9dica Populacional Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pricila","family":"Bernardi","sequence":"additional","affiliation":[{"name":"N\u00facleo de Gen\u00e9tica Cl\u00ednica Departamento de Cl\u00ednica M\u00e9dica Hospital Universit\u00e1rio Universidade Federal de Santa Catarina Florian\u00f3polis Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hector N.","family":"Seu\u00e1nez","sequence":"additional","affiliation":[{"name":"Programa de Gen\u00e9tica Instituto Nacional de C\u00e2ncer Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel \u00c2ngelo Martins","family":"Moreira","sequence":"additional","affiliation":[{"name":"Programa de Gen\u00e9tica Instituto Nacional de C\u00e2ncer Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I\u00eada Maria","family":"Orioli","sequence":"additional","affiliation":[{"name":"Estudo Colaborativo Latino Americano de Malforma\u00e7\u00f5es Cong\u00eanitas (ECLAMC) Departamento de Gen\u00e9tica Universidade Federal do Rio de Janeiro  Brazil"},{"name":"INAGEMP \u2013 Instituto Nacional de Gen\u00e9tica M\u00e9dica Populacional Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,2,12]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2012.08.012"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2004.01.004"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2006.02.011"},{"key":"e_1_2_5_5_1","first-page":"431","article-title":"Middle interhemispheric fusion: an unusual variant of holoprosencephaly","volume":"14","author":"Barkovich AJ","year":"1993","journal-title":"AJNR Am J Neuroradiol"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi037"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.8.791"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/2484"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0714-06.2006"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320340232"},{"key":"e_1_2_5_11_1","first-page":"443","article-title":"No association of the polyhistidine tract polymorphism of the ZIC2 gene with neural tube defects in a South American (ECLAMC) population","volume":"1","author":"Costa\u2010Lima MA","year":"2008","journal-title":"Mol Med Rep"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000104278"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.34.2.256"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20056"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.004325"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2010.09.005"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-013-1285-5"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2007.11.080"},{"key":"e_1_2_5_19_1","first-page":"529","article-title":"The kaleidoscopic world of rare craniofacial clefts: order out of chaos (Tessier classification)","volume":"3","author":"Kawamoto HK","year":"1976","journal-title":"Clin Plast Surg"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2008.063818"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30110"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1708"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.PRS.0000101540.32533.EC"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.517009"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2011-100339"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.21098"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.4.1618"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.13.2479"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32104"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390100537"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000637-198705000-00004"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2010.70"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34261"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34029"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23047"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32845"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0039026"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20982"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2012.01.005"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.037820"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006534-199601000-00048"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(70)80374-2"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.073049"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.30240"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A3415"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1387\/ijdb.072327as"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.otc.2006.10.008"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0503(76)80013-6"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33903"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn197"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32844"}],"container-title":["Birth Defects Research Part A: Clinical and Molecular Teratology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbdra.23216","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdra.23216","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bdra.23216","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdra.23216","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T03:44:58Z","timestamp":1693194298000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdra.23216"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,2,12]]},"references-count":50,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2014,4]]}},"alternative-id":["10.1002\/bdra.23216"],"URL":"https:\/\/doi.org\/10.1002\/bdra.23216","archive":["Portico"],"relation":{},"ISSN":["1542-0752","1542-0760"],"issn-type":[{"value":"1542-0752","type":"print"},{"value":"1542-0760","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,2,12]]}}}