{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:58:34Z","timestamp":1790974714268,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2006,8,24]],"date-time":"2006-08-24T00:00:00Z","timestamp":1156377600000},"content-version":"vor","delay-in-days":84,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2006,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>BACKGROUND:<\/jats:bold> CYP26A1, together with CYP26B1 and CYP26C1, are key enzymes of all\u2010<jats:italic>trans<\/jats:italic> retinoic acid (RA) inactivation and their specific and restricted expression in developing embryos participate in the fine tuning RA levels. As RA is a critical regulator of gene expression during embryonic development, the imbalance between the synthesis and degradation of RA during embryogenesis could contribute to malformations and developmental defects. <jats:bold>METHODS:<\/jats:bold> A PCR\u2013single strand conformation polymorphism (PCR\u2010SSCP) strategy was developed to screen for <jats:italic>CYP26A1<\/jats:italic> sequence variations that could affect the enzyme expression and\/or activity and applied to DNA samples from 80 unrelated Caucasians, comprising 40 French healthy volunteers and 40 Italian patients with spina bifida. The consequence of the 1\u2010bp deletion identified in the coding sequence was investigated by an in vitro functional assay using COS\u20107 cells. <jats:bold>RESULTS:<\/jats:bold> A total of 7 polymorphisms were identified, comprising 1 nucleotide deletion in the coding sequence (g.3116delT) that results in a frameshift and consequently in the creation of a premature stop codon. The g.3116delT mutation is of particular interest because it was identified in a patient with spina bifida and likely encodes a truncated protein with no enzymatic activity, as demonstrated by our preliminary in vitro data. <jats:bold>CONCLUSIONS:<\/jats:bold> Despite the fact that our findings could not show any evidence that the CYP26A1 genetic polymorphism has implications in the pathogenesis of spina bifida, this work represents the first description of a functional genetic polymorphism affecting the coding sequence of the human <jats:italic>CYP26A1<\/jats:italic> gene. Birth Defects Research (Part A) 76:491\u2013498, 2006. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/bdra.20275","type":"journal-article","created":{"date-parts":[[2006,8,24]],"date-time":"2006-08-24T20:02:17Z","timestamp":1156449737000},"page":"491-498","source":"Crossref","is-referenced-by-count":23,"title":["Evidence for a functional genetic polymorphism of the human retinoic acid\u2013metabolizing enzyme CYP26A1, an enzyme that may be involved in spina bifida"],"prefix":"10.1002","volume":"76","author":[{"given":"Emmanuel","family":"Rat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Billaut\u2010Laden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Allorge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Marc","family":"Lo\u2010Guidice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Tellier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christelle","family":"Cauffiez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Jonckheere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"van Seuningen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Lhermitte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Romano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Louis","family":"Gu\u00e9ant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck","family":"Broly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,8,24]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.855001"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-199512000-00006"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.03.092"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390000444"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20183"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390100505"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.14.4163"},{"key":"e_1_2_6_9_1","first-page":"443","volume-title":"Cellular biology and biochemistry of the retinoids","author":"Gudas LJ","year":"1994"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(03)00468-3"},{"key":"e_1_2_6_11_1","doi-asserted-by":"crossref","first-page":"17209","DOI":"10.1016\/S0021-9258(17)44890-3","article-title":"Multiple mutations of the human cytochrome P450IID6 gene (CYP2D6) in poor metabolizers of debrisoquine. Study of the functional significance of individual mutations by expression of chimeric genes","volume":"5","author":"Kagimoto M","year":"1990","journal-title":"J Biol Chem"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00210743"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-200207000-00004"},{"key":"e_1_2_6_14_1","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1210\/mend.14.9.0518","article-title":"Cytochrome P450RAI (CYP26) promoter: a distinct composite retinoic acid response element underlies the complex regulation of retinoic acid metabolism","volume":"14","author":"Loudig O","year":"2000","journal-title":"Mol Endocrinol"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(01)00463-4"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.58.6.1341"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02353473"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng876"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.252626599"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0602-221"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.30.18702"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20025"},{"key":"e_1_2_6_23_1","doi-asserted-by":"crossref","first-page":"6296","DOI":"10.1016\/S0021-9258(18)50362-8","article-title":"In vitro metabolism of retinoic acid in hamster intestine and liver","volume":"254","author":"Roberts AB","year":"1979","journal-title":"J Biol Chem"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2000.80.3.1021"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.851501"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1993.1193"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420050115"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nu.15.070195.000551"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.2133\/dmpk.17.374"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1999.9487"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M308337200"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.47.29922"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.30.18538"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1997.5157"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.120161397"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-7580.2003.00230.x"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(04)00062-0"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420340106"}],"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.20275","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdra.20275","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T02:34:31Z","timestamp":1697510071000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdra.20275"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,6]]},"references-count":37,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2006,6]]}},"alternative-id":["10.1002\/bdra.20275"],"URL":"https:\/\/doi.org\/10.1002\/bdra.20275","archive":["Portico"],"relation":{},"ISSN":["1542-0752","1542-0760"],"issn-type":[{"value":"1542-0752","type":"print"},{"value":"1542-0760","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,6]]}}}