{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T03:53:00Z","timestamp":1767844380660,"version":"3.49.0"},"reference-count":28,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2015,9,26]],"date-time":"2015-09-26T00:00:00Z","timestamp":1443225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["MOP-115189"],"award-info":[{"award-number":["MOP-115189"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>A single nucleotide polymorphism (SNP) in the synthetase domain of the trifunctional folate\u2010dependent enzyme <jats:italic>MTHFD1<\/jats:italic> (c.1958G&gt;A, R653Q) has been linked to adverse pregnancy outcomes, neural tube defects, and possibly congenital heart defects. Maternal folate deficiency may also modify the risk associated with these disorders. We recently established a mouse model with a mild deficiency of 10\u2010formyltetrahydrofolate synthetase activity in MTHFD1 (<jats:italic>Mthfd1S<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mice) to investigate disorders associated with SNPs in this gene. The effect of synthetase deficiency on embryonic heart development has not yet been examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Female <jats:italic>Mthfd1S<\/jats:italic><jats:sup>+\/+<\/jats:sup> and <jats:sup>+\/\u2010<\/jats:sup> mice were placed on control and folate\u2010deficient diets for 6 weeks before mating to <jats:italic>Mthfd1S<\/jats:italic><jats:sup>+\/\u2010<\/jats:sup> males. Embryos and placentae were collected at embryonic day 14.5. Embryos were evaluated for congenital heart defects by histological examination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Embryonic <jats:italic>Mthfd1S<\/jats:italic><jats:sup>+\/\u2010<\/jats:sup> genotype was associated with an increased incidence of heart defects, primarily ventricular septal defects. Other markers of embryonic development (crown\u2010rump length, embryonic weight, embryonic delay, placental weight, and thickness of the ventricular myocardium) were not affected by embryonic genotype. Maternal genotype and diet did not have a significant effect on these outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Deficiency of the MTHFD1 10\u2010formyltetrahydrofolate synthetase activity in embryos is associated with increased incidence of congenital heart defects. Birth Defects Research (Part A) 103:1031\u20131038, 2015. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.23451","type":"journal-article","created":{"date-parts":[[2015,9,26]],"date-time":"2015-09-26T11:35:50Z","timestamp":1443267350000},"page":"1031-1038","source":"Crossref","is-referenced-by-count":19,"title":["MTHFD1 formyltetrahydrofolate synthetase deficiency, a model for the MTHFD1 R653Q variant, leads to congenital heart defects in mice"],"prefix":"10.1002","volume":"103","author":[{"given":"Karen E.","family":"Christensen","sequence":"first","affiliation":[{"name":"Departments of Human Genetics and Pediatrics McGill University, and the Research Institute of the McGill University Health Centre Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liyuan","family":"Deng","sequence":"additional","affiliation":[{"name":"Departments of Human Genetics and Pediatrics McGill University, and the Research Institute of the McGill University Health Centre Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renata H.","family":"Bahous","sequence":"additional","affiliation":[{"name":"Departments of Human Genetics and Pediatrics McGill University, and the Research Institute of the McGill University Health Centre Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loydie A.","family":"Jerome\u2010Majewska","sequence":"additional","affiliation":[{"name":"Departments of Human Genetics and Pediatrics McGill University, and the Research Institute of the McGill University Health Centre Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rima","family":"Rozen","sequence":"additional","affiliation":[{"name":"Departments of Human Genetics and Pediatrics McGill University, and the Research Institute of the McGill University Health Centre Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,9,26]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/81.5.1213"},{"key":"e_1_2_6_3_1","unstructured":"BatesD MaechlerM BolkerBM WalkerS.2014.lme4: linear mixed\u2010effects models using Eigen and S4. 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