{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T20:50:55Z","timestamp":1792615855287,"version":"4.5.0"},"reference-count":113,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2012,9,28]],"date-time":"2012-09-28T00:00:00Z","timestamp":1348790400000},"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":[[2012,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A variety of human birth defects originate in failure of closure of the embryonic neural tube. The genetic cause of the most common nonsyndromic defects, spina bifida (SB) or anencephaly, is considered to be combinations of variants at multiple genes. The genes contributing to the etiology of neural tube closure defects (NTDs) are unknown. Mutations in planar cell polarity (PCP) genes in mice cause a variety of defects including the NTD, craniorachischisis, and sometimes SB or exencephaly (EX); they also demonstrate the role of digenic combinations of PCP mutants in NTDs. Recent studies have sought rare predicted\u2010to\u2010be\u2010deleterious alterations (putative mutations) in coding sequence of PCP genes in human cases with various anomalies of the neural tube. This review summarizes the cumulative results of these studies according to a framework based on the embryopathogenesis of NTDs, and considers some of the insights from the approaches used and the limitations. Rare putative mutations in the PCP genes<jats:italic>VANGL2<\/jats:italic>,<jats:italic>SCRIB<\/jats:italic>,<jats:italic>DACT1<\/jats:italic>, and<jats:italic>CELSR1<\/jats:italic>cumulatively contributed to over 20% of cases with craniorachischisis, a rare defect; no contributing variants were found for<jats:italic>PRICKLE1<\/jats:italic>or<jats:italic>PTK7<\/jats:italic>. PCP rare putative mutations had a weaker role in myelomeningocele (SB), being found in approximately 6% of cases and cumulated across<jats:italic>CELSR1<\/jats:italic>,<jats:italic>FUZ<\/jats:italic>,<jats:italic>FZD6<\/jats:italic>,<jats:italic>PRICKLE1<\/jats:italic>,<jats:italic>VANGL1<\/jats:italic>, and<jats:italic>VANGL2<\/jats:italic>. These results demonstrate that PCP gene alterations contribute to the etiology of human NTDs. We recommend that future research should explore other types of PCP gene variant such as regulatory mutations and low frequency (1 to 5%) deleterious polymorphisms. Birth Defects Research (Part A) 2012. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/bdra.23079","type":"journal-article","created":{"date-parts":[[2012,9,30]],"date-time":"2012-09-30T13:32:08Z","timestamp":1349011928000},"page":"824-840","source":"Crossref","is-referenced-by-count":147,"title":["A consideration of the evidence that genetic defects in planar cell polarity contribute to the etiology of human neural tube defects"],"prefix":"10.1002","volume":"94","author":[{"given":"Diana M.","family":"Juriloff","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muriel J.","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,9,28]]},"reference":[{"key":"e_1_2_2_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23002"},{"key":"e_1_2_2_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008999"},{"key":"e_1_2_2_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2956"},{"key":"e_1_2_2_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2042"},{"key":"e_1_2_2_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21589"},{"key":"e_1_2_2_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2010.06.008"},{"key":"e_1_2_2_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(69)92130-8"},{"issue":"6","key":"e_1_2_2_9_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1469-8749.1974.tb03442.x","article-title":"Clues to the aetiology of neural tube malformations","volume":"16","author":"Carter CO","year":"1974","journal-title":"Dev Med Child Neurol"},{"key":"e_1_2_2_10_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1994.1230"},{"key":"e_1_2_2_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(03)00212-1"},{"key":"e_1_2_2_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1181"},{"key":"e_1_2_2_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(03)00374-9"},{"key":"e_1_2_2_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199212243272602"},{"key":"e_1_2_2_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.21.6.413"},{"key":"e_1_2_2_16_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00448"},{"key":"e_1_2_2_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21643"},{"key":"e_1_2_2_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30766"},{"key":"e_1_2_2_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000259"},{"key":"e_1_2_2_20_1","first-page":"299","volume-title":"Introduction to Quantitative Genetics","author":"Falconer DS","year":"1996"},{"key":"e_1_2_2_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2011.01.001"},{"key":"e_1_2_2_22_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.054080"},{"key":"e_1_2_2_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1966"},{"key":"e_1_2_2_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2011.06.011"},{"key":"e_1_2_2_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.2206"},{"key":"e_1_2_2_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(98)00029-X"},{"key":"e_1_2_2_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9926(199611)54:5<230::AID-TERA3>3.0.CO;2-3"},{"key":"e_1_2_2_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0402802101"},{"key":"e_1_2_2_29_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00164"},{"key":"e_1_2_2_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20333"},{"key":"e_1_2_2_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20676"},{"key":"e_1_2_2_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420500109"},{"key":"e_1_2_2_33_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.025767"},{"key":"e_1_2_2_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/35011068"},{"key":"e_1_2_2_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20792"},{"key":"e_1_2_2_36_1","doi-asserted-by":"publisher","DOI":"10.1161\/hh1301.092497"},{"key":"e_1_2_2_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.22696"},{"key":"e_1_2_2_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.22130"},{"key":"e_1_2_2_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.10143"},{"key":"e_1_2_2_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.6.993"},{"key":"e_1_2_2_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21026"},{"key":"e_1_2_2_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2010.01515.x"},{"key":"e_1_2_2_43_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa060651"},{"key":"e_1_2_2_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/90081"},{"key":"e_1_2_2_45_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc0910820"},{"key":"e_1_2_2_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80354-2"},{"key":"e_1_2_2_47_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.028076"},{"key":"e_1_2_2_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02677"},{"key":"e_1_2_2_49_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00520"},{"key":"e_1_2_2_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08494"},{"key":"e_1_2_2_51_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.057166"},{"issue":"41","key":"e_1_2_2_52_1","first-page":"1","article-title":"Sec24b selectively sorts Vangl2 to regulate planar cell polarity during neural tube closure","volume":"12","author":"Merte J","year":"2010","journal-title":"Nat Cell Biol"},{"key":"e_1_2_2_53_1","unstructured":"Mouse Genome Informatics.2012. The Jackson Laboratory Bar Harbor Maine. Available at:http:\/\/www.informatics.jax.org. Accessed May 1 2012."},{"key":"e_1_2_2_54_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.epirev.a017947"},{"key":"e_1_2_2_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19971212)73:2<113::AID-AJMG2>3.0.CO;2-V"},{"key":"e_1_2_2_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9926(199806)57:6<302::AID-TERA3>3.0.CO;2-Y"},{"key":"e_1_2_2_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)90133-A"},{"key":"e_1_2_2_58_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.22.2593"},{"key":"e_1_2_2_59_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg014"},{"key":"e_1_2_2_60_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2001.6638"},{"key":"e_1_2_2_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20686"},{"key":"e_1_2_2_62_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvp254"},{"key":"e_1_2_2_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.02.025"},{"key":"e_1_2_2_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/374350a0"},{"key":"e_1_2_2_65_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-213X-10-87"},{"key":"e_1_2_2_66_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.106.142406"},{"key":"e_1_2_2_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2007.09.054"},{"key":"e_1_2_2_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2007.03.011"},{"key":"e_1_2_2_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mod.2009.12.002"},{"key":"e_1_2_2_70_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-96327-8"},{"key":"e_1_2_2_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21662"},{"key":"e_1_2_2_72_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20693"},{"key":"e_1_2_2_73_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.053660"},{"key":"e_1_2_2_74_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.179"},{"key":"e_1_2_2_75_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20369"},{"key":"e_1_2_2_76_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.056622"},{"key":"e_1_2_2_77_1","doi-asserted-by":"publisher","DOI":"10.1203\/pdr.0b013e3180323810"},{"key":"e_1_2_2_78_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.GIM.0000151158.09278.2B"},{"key":"e_1_2_2_79_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr359"},{"key":"e_1_2_2_80_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22121"},{"key":"e_1_2_2_81_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1552"},{"key":"e_1_2_2_82_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genet.42.110807.091432"},{"key":"e_1_2_2_83_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09129"},{"key":"e_1_2_2_84_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.435"},{"key":"e_1_2_2_85_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.10.2227"},{"key":"e_1_2_2_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2012.01.025"},{"key":"e_1_2_2_87_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0901332106"},{"key":"e_1_2_2_88_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm961"},{"key":"e_1_2_2_89_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1428"},{"key":"e_1_2_2_90_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2555"},{"key":"e_1_2_2_91_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0712126105"},{"key":"e_1_2_2_92_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002340000325"},{"key":"e_1_2_2_93_1","doi-asserted-by":"publisher","DOI":"10.1038\/35011077"},{"key":"e_1_2_2_94_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00123"},{"key":"e_1_2_2_95_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02347"},{"key":"e_1_2_2_96_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1622"},{"key":"e_1_2_2_97_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4698-05.2005"},{"key":"e_1_2_2_98_1","doi-asserted-by":"crossref","first-page":"4761","DOI":"10.1523\/JNEUROSCI.21-13-04761.2001","article-title":"Progressive cerebellar, auditory, and esophageal dysfunction caused by targeted disruption of the frizzled\u20104 gene","volume":"21","author":"Wang Y","year":"2001","journal-title":"J Neurosci"},{"key":"e_1_2_2_99_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-19-08563.2002"},{"key":"e_1_2_2_100_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.2009.28858"},{"key":"e_1_2_2_101_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.041434"},{"key":"e_1_2_2_102_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019357"},{"key":"e_1_2_2_103_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00407"},{"key":"e_1_2_2_104_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.085381"},{"key":"e_1_2_2_105_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33230"},{"key":"e_1_2_2_106_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.6.1211"},{"key":"e_1_2_2_107_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2008.05.007"},{"key":"e_1_2_2_108_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq397"},{"key":"e_1_2_2_109_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq104"},{"key":"e_1_2_2_110_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.129.10.2507"},{"key":"e_1_2_2_111_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.000380"},{"key":"e_1_2_2_112_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8480178"},{"key":"e_1_2_2_113_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.052001"},{"key":"e_1_2_2_114_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2010.01.003"}],"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.23079","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdra.23079","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T22:30:39Z","timestamp":1714429839000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdra.23079"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,9,28]]},"references-count":113,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2012,10]]}},"alternative-id":["10.1002\/bdra.23079"],"URL":"https:\/\/doi.org\/10.1002\/bdra.23079","archive":["Portico"],"relation":{},"ISSN":["1542-0752","1542-0760"],"issn-type":[{"value":"1542-0752","type":"print"},{"value":"1542-0760","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,9,28]]}}}