{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T22:53:59Z","timestamp":1790376839178,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T00:00:00Z","timestamp":1676851200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Rare mutations in multiple genes have been associated with human neural tube defects (NTDs), but their causative roles in NTDs disease are poorly understood. Insufficiency of the ribosomal biogenesis gene treacle ribosome biogenesis factor 1(<jats:italic>Tcof1<\/jats:italic>) results in cranial NTDs and craniofacial malformations in mice. Here, we aimed to identify genetic association of <jats:italic>TCOF1<\/jats:italic> with human NTDs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>High\u2010throughput sequencing targeted on <jats:italic>TCOF1<\/jats:italic>\u00a0was performed on samples from 355\u00a0human\u00a0cases affected by NTDs and 225 controls from a Han Chinese population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Four novel missense variants were found in the NTD cohort. Cell\u2010based assays indicated that the p.(A491G) variant carried by an individual, who shows anencephaly and single\u2010nostril abnormality, attenuates production of total proteins, suggesting a loss\u2010of\u2010function mutation in ribosomal biogenesis. Importantly, this variant promotes nucleolar disruption and stabilizes p53 protein, highlighting an unbalancing effect on cell apoptosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study explored the functional impact of a missense variant in <jats:italic>TCOF1<\/jats:italic>, implicating a set of novel causative biological factors involved in the pathogenicity of human NTDs, particularly whom combined with craniofacial abnormality.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2150","type":"journal-article","created":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T04:06:26Z","timestamp":1676952386000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Genetic mutations in ribosomal biogenesis gene <scp><i>TCOF1<\/i><\/scp> identified in human neural tube defects"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8049-0120","authenticated-orcid":false,"given":"Fang","family":"Wang","sequence":"first","affiliation":[{"name":"Beijing Municipal Key Laboratory of Child Development and Nutriomics Capital Institute of Pediatrics  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiqin","family":"Cheng","sequence":"additional","affiliation":[{"name":"Beijing Municipal Key Laboratory of Child Development and Nutriomics Capital Institute of Pediatrics  Beijing China"},{"name":"Department of Biochemistry and Molecular Biology, Ministry of Education Key Laboratory of Cellular Physiology Shanxi Medical University  Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4597-7697","authenticated-orcid":false,"given":"Qin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Municipal Key Laboratory of Child Development and Nutriomics Capital Institute of Pediatrics  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0093-1927","authenticated-orcid":false,"given":"Jin","family":"Guo","sequence":"additional","affiliation":[{"name":"Beijing Municipal Key Laboratory of Child Development and Nutriomics Capital Institute of Pediatrics  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,2,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2015.02.007"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1017935108"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2184"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035\u2010016\u20100164\u20100"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422\u2010018\u20100061\u20103"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102350\u201012\u2010125"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(13)70110\u20108"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.10.1473"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.5.727"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603730103"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601\u20106343.2007.00388.x"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2014.04.014"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi208"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00412\u2010013\u20100430\u20100"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20397"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2013.09.016"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1725"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.bmb.a071187"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.169797"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/09603123.2010.491854"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0028408"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.30057"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg579"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2017.0234"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2012"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0402492101"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8101198"},{"issue":"1","key":"e_1_2_11_29_1","first-page":"1","article-title":"Updated estimates of neural tube defects prevented by mandatory folic acid fortification \u2010 United States, 1995\u20102011","volume":"64","author":"Williams J.","year":"2015","journal-title":"Morbidity and Mortality Weekly Report"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.7.3110"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw1208"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201104057"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0895\u20103988(08)60005\u20107"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13064\u2010020\u201000145\u20107"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.2150","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.2150","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.2150","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T07:47:52Z","timestamp":1692517672000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.2150"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,20]]},"references-count":33,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,5]]}},"alternative-id":["10.1002\/mgg3.2150"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.2150","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,20]]},"assertion":[{"value":"2022-05-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2150"}}