{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:57:26Z","timestamp":1791208646957,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2015,9,14]],"date-time":"2015-09-14T00:00:00Z","timestamp":1442188800000},"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":[[2015,12]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Neural tube defects (NTDs) are among the most common congenital defects affecting approximately 1 in 1000 live births in North America. Their etiology is complex including environmental and genetic factors. Defects in the planar cell polarity (PCP) signaling pathway have been strongly associated with NTDs in animal models and human cohorts. <jats:italic>Protein tyrosine kinase 7<\/jats:italic> (<jats:italic>Ptk7<\/jats:italic>) was shown to cause a very severe form of NTDs called craniorachischisis in a mouse model and genetically interacts with a core PCP member <jats:italic>Vangl2<\/jats:italic> where double heterozygotes suffer from spina bifida. In this study, we examined the role of <jats:italic>PTK7<\/jats:italic> in human NTDs to determine whether variants 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>PTK7<\/jats:italic> in a cohort of 473 patients affected with various forms of open and closed NTDs. Novel and rare variants(&lt;1%) were genotyped in a cohort of 473 individuals. Their pathogenic effect was predicted in silico and functionally in an overexpression assay in a well\u2010established zebrafish model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified in our cohort 6 rare variants, 3 of which were absent in public databases. One variant, p.Gly348Ser, acted as a hypermorph when overexpressed in the zebrafish model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We detected potentially pathogenic <jats:italic>PTK7<\/jats:italic> variants in 1.1% of our NTD cohort. Our findings implicate <jats:italic>PTK7<\/jats:italic> as a risk factor for NTDs and provide additional evidence for a pathogenic role of PCP signaling in these malformations. Birth Defects Research (Part A), 103:1021\u20131027, 2015. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.23422","type":"journal-article","created":{"date-parts":[[2015,9,14]],"date-time":"2015-09-14T15:09:46Z","timestamp":1442243386000},"page":"1021-1027","source":"Crossref","is-referenced-by-count":33,"title":["Role of the planar cell polarity gene <i>Protein tyrosine kinase 7<\/i> in neural tube defects in humans"],"prefix":"10.1002","volume":"103","author":[{"given":"Mingqin","family":"Wang","sequence":"first","affiliation":[{"name":"CHU Ste\u2010Justine Research Center Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"De Marco","sequence":"additional","affiliation":[{"name":"Istituto Giannina Gaslini Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Merello","sequence":"additional","affiliation":[{"name":"Istituto Giannina Gaslini Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Drapeau","sequence":"additional","affiliation":[{"name":"Department of Neurosciences University of Montr\u00e9al, Montr\u00e9al Qu\u00e9bec Canada"},{"name":"CHUM Research Center Montr\u00e9al Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Capra","sequence":"additional","affiliation":[{"name":"Istituto Giannina Gaslini Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoha","family":"Kibar","sequence":"additional","affiliation":[{"name":"CHU Ste\u2010Justine Research Center Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Department of Neurosciences University of Montr\u00e9al, Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,9,14]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23002"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23273"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.spen.2009.06.001"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21589"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23255"},{"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":"10.1038\/ncomms5777"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.090183"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23079"},{"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":"10.1038\/nmeth1010"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02677"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)90133-A"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2011.236"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2011.12.019"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mod.2009.12.002"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejrad.2003.10.015"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2009.09.004"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.023556"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genet.42.110807.091432"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/gm13"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.073007"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.30054"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.056291"}],"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.23422","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdra.23422","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T20:59:03Z","timestamp":1696625943000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdra.23422"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,9,14]]},"references-count":24,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2015,12]]}},"alternative-id":["10.1002\/bdra.23422"],"URL":"https:\/\/doi.org\/10.1002\/bdra.23422","archive":["Portico"],"relation":{},"ISSN":["1542-0752","1542-0760"],"issn-type":[{"value":"1542-0752","type":"print"},{"value":"1542-0760","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,9,14]]}}}