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Although extensively investigated, the genetic etiology of NTDs remains poorly understood. FKBP8 is critical for proper mammalian neural tube closure. Fkbp8\u2212\/\u2212 mouse embryos showed posterior NTDs consistent with a diagnosis of spina bifida (SB). To date, no publication has reported any association between FKBP8 and human NTDs. Using Sanger sequencing on genomic DNA samples from 472 SB and 565 control samples, we identified five rare (MAF\u00a0\u2264\u00a00.001) deleterious variants in SB patients, while no rare deleterious variant was identified in the controls (P\u2009=\u20090.0191). p.Glu140* affected FKBP8 localization to the mitochondria and created a truncated form of the FKBP8 protein, thus impairing its interaction with BCL2 and ultimately leading to an increase in cellular apoptosis. p.Ser3Leu, p.Lys315Asn and p.Ala292Ser variants decreased FKBP8 protein level. p.Lys315Asn further increased the cellular apoptosis. RNA sequencing on anterior and posterior tissues isolated from Fkbp8\u2212\/\u2212 and wildtype mice at E9.5 and E10.5 showed that Fkbp8\u2212\/\u2212 embryos have an abnormal expression profile within tissues harvested at posterior sites, thus leading to a posterior NTD. Moreover, we found that Fkbp8 knockout mouse embryos have abnormal expression of Wnt3a and Nkx2.9 during the early stage of neural tube development, perhaps also contributing to caudal specific NTDs. These findings provide evidence that functional variants of FKBP8 are risk factors for SB, which may involve a novel mechanism by which Fkbp8 mutations specifically cause SB in mice.<\/jats:p>","DOI":"10.1093\/hmg\/ddaa211","type":"journal-article","created":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T15:19:15Z","timestamp":1600442355000},"page":"3132-3144","source":"Crossref","is-referenced-by-count":11,"title":["FKBP8 variants are risk factors for spina bifida"],"prefix":"10.1093","volume":"29","author":[{"given":"Tian","family":"Tian","sequence":"first","affiliation":[{"name":"Institute of Reproductive and Child Health, National Health Commission Key Laboratory of Reproductive Health, Peking University, Beijing 100191, China"},{"name":"Center for Precision Environmental Health, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77031, 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Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77031, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert M","family":"Cabrera","sequence":"additional","affiliation":[{"name":"Center for Precision Environmental Health, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77031, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menuka","family":"Karki","sequence":"additional","affiliation":[{"name":"Center for Precision Environmental Health, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77031, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J","family":"Marini","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan N","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Center for Precision Environmental Health, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77031, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Han","sequence":"additional","affiliation":[{"name":"Center for Precision Environmental Health, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77031, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The University of Texas at Austin Dell Medical School, Austin, TX 78723, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2033-9277","authenticated-orcid":false,"given":"Linlin","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Child Health, National Health Commission Key Laboratory of Reproductive Health, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogdan J","family":"Wlodarczyk","sequence":"additional","affiliation":[{"name":"Center for Precision Environmental Health, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77031, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary M","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9115-5638","authenticated-orcid":false,"given":"Aiguo","family":"Ren","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Child Health, National Health Commission Key Laboratory of Reproductive Health, Peking University, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard H","family":"Finnell","sequence":"additional","affiliation":[{"name":"Center for Precision Environmental Health, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77031, USA"},{"name":"Departments of Molecular and Human Genetics and Medicine, Baylor College of Medicine, Houston, TX 77031, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1504-0884","authenticated-orcid":false,"given":"Yunping","family":"Lei","sequence":"additional","affiliation":[{"name":"Center for 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Genet."},{"key":"2020110605013721500_ref27","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1111\/j.1365-2443.2008.01194.x","article-title":"Regulation of apoptosis and neurite extension by FKBP38 is required for neural tube formation in the mouse","volume":"13","author":"Shirane","year":"2008","journal-title":"Genes Cells"},{"key":"2020110605013721500_ref28","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1007\/s00381-014-2428-1","article-title":"A critical role of noggin in developing folate-nonresponsive NTD in Fkbp8 \u2212\/\u2212 embryos","volume":"30","author":"Tsurubuchi","year":"2014","journal-title":"Childs Nerv. Syst."},{"key":"2020110605013721500_ref29","first-page":"170","article-title":"Apoptosis: molecular mechanisms in programmed cell death","volume":"56","author":"Fesus","year":"1991","journal-title":"Eur. J. Cell Biol."},{"key":"2020110605013721500_ref30","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1158\/1535-7163.MCT-08-0895","article-title":"Regulated cell death pathways: new twists in modulation of BCL2 family function","volume":"8","author":"Sasi","year":"2009","journal-title":"Mol. Cancer Ther."},{"key":"2020110605013721500_ref31","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1002\/humu.22750","article-title":"Rare LRP6 variants identified in spina bifida patients","volume":"36","author":"Lei","year":"2015","journal-title":"Hum. Mutat."},{"key":"2020110605013721500_ref32","doi-asserted-by":"crossref","first-page":"12843","DOI":"10.1073\/pnas.0501963102","article-title":"Crooked tail (cd) model of human folate-responsive neural tube defects is mutated in Wnt coreceptor lipoprotein receptor-related protein 6","volume":"102","author":"Carter","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2020110605013721500_ref33","doi-asserted-by":"crossref","first-page":"4267","DOI":"10.1093\/hmg\/ddt277","article-title":"LRP6 exerts non-canonical effects on Wnt signaling during neural tube closure","volume":"22","author":"Gray","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"2020110605013721500_ref34","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nn0602-854","article-title":"Progressive induction of caudal neural character by graded Wnt signaling","volume":"5","author":"Nordstrom","year":"2002","journal-title":"Nat. Neurosci."},{"key":"2020110605013721500_ref35","doi-asserted-by":"crossref","first-page":"13713","DOI":"10.1073\/pnas.94.25.13713","article-title":"Regulation of dorsal fate in the neuraxis by Wnt-1 and Wnt-3a","volume":"94","author":"Saint-Jeannet","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2020110605013721500_ref36","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/nn1068","article-title":"Specification of dorsal telencephalic character by sequential Wnt and FGF signaling","volume":"6","author":"Gunhaga","year":"2003","journal-title":"Nat. Neurosci."},{"key":"2020110605013721500_ref37","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1007\/s003350010089","article-title":"Conserved linkage of NK-2 homeobox gene pairs Nkx2-2\/2-4 and Nkx2-1\/2-9 in mammals","volume":"11","author":"Wang","year":"2000","journal-title":"Mamm. Genome"},{"key":"2020110605013721500_ref38","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1038\/nn1104","article-title":"Lmx1b is essential for the development of serotonergic neurons","volume":"6","author":"Ding","year":"2003","journal-title":"Nat. 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Cell Biol."},{"key":"2020110605013721500_ref40","doi-asserted-by":"crossref","first-page":"3276","DOI":"10.1111\/febs.14970","article-title":"Apoptotic cell death regulation in neurons","volume":"286","author":"Hollville","year":"2019","journal-title":"FEBS J."},{"key":"2020110605013721500_ref41","doi-asserted-by":"crossref","first-page":"e38014","DOI":"10.7554\/eLife.38014","article-title":"Decoupling the impact of microRNAs on translational repression versus RNA degradation in embryonic stem cells","volume":"7","author":"Jacob","year":"2018","journal-title":"elife"},{"key":"2020110605013721500_ref42","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1111\/j.1365-3016.1991.tb00728.x","article-title":"Birth defects monitoring in California: a resource for epidemiological research","volume":"5","author":"Croen","year":"1991","journal-title":"Paediatr. Perinat. Epidemiol."},{"key":"2020110605013721500_ref43","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1002\/humu.23969","article-title":"Loss of RAD9B impairs early neural development and contributes to the risk for human spina bifida","volume":"41","author":"Cao","year":"2020","journal-title":"Hum. Mutat."},{"key":"2020110605013721500_ref44","doi-asserted-by":"crossref","first-page":"44117","DOI":"10.1074\/jbc.M101958200","article-title":"Transient expression of wild-type or mitochondrially targeted Bcl-2 induces apoptosis, whereas transient expression of endoplasmic reticulum-targeted Bcl-2 is protective against Bax-induced cell death","volume":"276","author":"Wang","year":"2001","journal-title":"J. Biol. Chem."},{"key":"2020110605013721500_ref45","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nbt.3519","article-title":"Near-optimal probabilistic RNA-seq quantification","volume":"34","author":"Bray","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"2020110605013721500_ref46","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. 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