{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:06:01Z","timestamp":1778717161147,"version":"3.51.4"},"reference-count":48,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2001,4,19]],"date-time":"2001-04-19T00:00:00Z","timestamp":987638400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Teratology"],"published-print":{"date-parts":[[2001,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Very little is known about the identity of genetic factors involved in the complex etiology of nonsyndromic neural tube defects (NTD). Potential susceptibility genes have emerged from the vast number of mutant mouse strains displaying NTD. Reasonable candidates are the human homologues of mice exencephaly genes <jats:italic>Tfap2<\/jats:italic>\u03b1 and <jats:italic>Msx2<\/jats:italic>, which are expressed in the developing neural tube.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A single\u2010strand conformation analysis (SSCA) mutation screen of the coding sequences of <jats:italic>TFAP2<\/jats:italic>\u03b1 and <jats:italic>MSX2<\/jats:italic> was performed for 204 nonsyndromic NTD patients including cases of anencephaly (n = 10), encephalocele (n = 8), and spina bifida aperta, SBA (n = 183). A selected number of SBA patients was additionally tested for specific mutations in <jats:italic>MTHFD<\/jats:italic>, <jats:italic>FR<\/jats:italic>\u03b1, and <jats:italic>PAX1<\/jats:italic> already shown to be related to NTD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two <jats:italic>TFAP2<\/jats:italic>\u03b1 point mutations in individual SBA patients were silent on the amino acid level (C308C, T396T). On nucleic acid level, these mutations change evolutionary conserved codons and thus may influence mRNA processing and translation efficiency. One SBA patient displayed an exonic 9\u2010bp deletion in <jats:italic>MSX2<\/jats:italic> leading to a shortened and possibly less functional protein. None of these mutations was found in 222 controls. Seven polymorphisms detected in <jats:italic>TFAP2<\/jats:italic>\u03b1 and <jats:italic>MSX2<\/jats:italic> were equally distributed in patients and controls. Patients with combined heterozygosity of an exonic <jats:italic>MSX2<\/jats:italic> and an intronic <jats:italic>TFAP2<\/jats:italic>\u03b1 polymorphism were at a slightly increased risk of NTD (OR 1.71; 95% CI 0.57\u20135.39).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Although several new genetic variants were found in <jats:italic>TFAP2<\/jats:italic> and <jats:italic>MSX2<\/jats:italic>, no statistically significant association was found between NTD cases and the new alleles or their combinations. Further studies are necessary to finally decide if these gene variants may have acted as susceptibility factors in our individual cases. Teratology 63:167\u2013175, 2001. \u00a9 2001 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/tera.1031","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T20:21:39Z","timestamp":1030306899000},"page":"167-175","source":"Crossref","is-referenced-by-count":13,"title":["A screen for mutations in human homologues of mice exencephaly genes <i>Tfap2<\/i>\u03b1 and <i>Msx2<\/i> in patients with neural tube 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