{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:44:10Z","timestamp":1791477850195,"version":"4.3.4"},"reference-count":22,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,2,28]],"date-time":"2012-02-28T00:00:00Z","timestamp":1330387200000},"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":[[2012,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Neural tube defects (NTDs), including anencephaly and spina bifida, have a complex etiology. Defects in the planar cell polarity (PCP) signaling pathway have been strongly associated with NTDs in animal models and human cohorts. In this genetic study, we examined the core PCP gene <jats:italic>CELSR1<\/jats:italic> in NTDs and caudal agenesis cases to determine whether mutations at this gene predispose to these defects.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We sequenced the coding region and the exon\u2010intron junctions of <jats:italic>CELSR1<\/jats:italic> in a cohort of 473 patients affected with various forms of open and closed NTDs (412) or caudal agenesis (61). Novel and rare variants (&lt;1%) were genotyped in a cohort of 639 ethnically\u2010matched individuals. The effect of novel missense mutations absent in controls and in public databases on protein function was predicted in silico.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>We identified in our cohort one nonsense mutation in exon 1 of <jats:italic>CELSR1<\/jats:italic> that truncates the majority of the protein in one patient with NTD and one in\u2010frame 12 bp deletion that removes a putative PKC phosphorylation \u201cSSR\u201d motif in one caudal agenesis patient. We also detected a total of 13 novel missense variants in 12 patients (11 NTDs and 1 caudal agenesis) that were predicted to be pathogenic in silico.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>We detected novel <jats:italic>CELSR1<\/jats:italic> mutations predicted to be pathogenic in 2.9% of our NTD cohort and 3.3% of our caudal agenesis cohort. Our findings implicate <jats:italic>CELSR1<\/jats:italic> as a risk factor for NTDs or caudal agenesis and provide additional evidence for a pathogenic role of PCP signaling in these malformations. Birth Defects Research (Part A), 2012. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.23002","type":"journal-article","created":{"date-parts":[[2012,2,28]],"date-time":"2012-02-28T11:08:27Z","timestamp":1330427307000},"page":"176-181","source":"Crossref","is-referenced-by-count":96,"title":["Role of the planar cell polarity gene <i>CELSR1<\/i> in neural tube defects and caudal agenesis"],"prefix":"10.1002","volume":"94","author":[{"given":"Redouane","family":"Allache","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"De Marco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Merello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Capra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoha","family":"Kibar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,2,28]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2393-1-8"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.spen.2009.06.001"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21589"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.04.048"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(03)00374-9"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21643"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ntt.2004.12.007"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2005.03.026"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21026"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2010.01515.x"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa060651"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21662"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0150-9861(04)96875-7"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ro.2006.07.001"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr359"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/gm13"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2043"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(01)00623-2"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2008.05.006"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002340000325"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80046-X"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33230"}],"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.23002","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdra.23002","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T12:57:30Z","timestamp":1700571450000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdra.23002"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,2,28]]},"references-count":22,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2012,3]]}},"alternative-id":["10.1002\/bdra.23002"],"URL":"https:\/\/doi.org\/10.1002\/bdra.23002","archive":["Portico"],"relation":{},"ISSN":["1542-0752","1542-0760"],"issn-type":[{"value":"1542-0752","type":"print"},{"value":"1542-0760","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,2,28]]}}}