{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T21:55:59Z","timestamp":1777672559641,"version":"3.51.4"},"reference-count":31,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T00:00:00Z","timestamp":1730160000000},"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":["Birth Defects Research"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Uninterrupted folate metabolism plays a vital role in embryonic development, ensuring a supply of one\u2010carbon\u2010activated folate cofactors for essential processes. Folate deficiency has been implicated in the development of orofacial clefts (OFC) and congenital heart disease (CHD). Although both malformations have been extensively studied in lieu of folate deficiency, the results of corresponding studies are ambiguous due to the interplay of maternal and fetal genomes controlling folate metabolism in the developing fetus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used the innovative study design to compare affected and unaffected siblings from the same mother, thus minimizing the effect of the maternal genome. Thus, it might be possible to identify genetic markers of congenital malformations that pertain exclusively to the child. This study compared demographic and environmental factors between OFC or CHD\u2010affected and unaffected pregnancies as well as the presence of polymorphisms in genes of folate metabolism between OFC or CHD\u2010affected and unaffected siblings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Only the maternal fever in the first trimester was a risk factor for OFC, whereas the maternal advanced age, medication administration, and common polymorphism in the <jats:italic>FPGS<\/jats:italic> gene increased the risk of CHD formation. Both OFC and CHD formation were associated with a higher number of variant loci in genes of folate\u2013methionine cycles.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Both OFC and CHD formation were associated with a higher number of mutated loci in genes of folate\u2013methionine cycles, indicating polygenic and possibly multifactorial inheritance.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.2408","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T09:41:33Z","timestamp":1730281293000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Higher Incidence of Common Polymorphisms in the Genes of Folate and Methionine Cycles in Children With Orofacial Clefs and Congenital Heart Defects Compared to their Unaffected Siblings"],"prefix":"10.1002","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7662-8481","authenticated-orcid":false,"given":"Nata\u0161a","family":"Karas\u00a0Ku\u017eeli\u010dki","sequence":"first","affiliation":[{"name":"Department of Clinical Biochemistry, Faculty of Pharmacy University of Ljubljana  Ljubljana Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alenka","family":"\u0160mid","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Faculty of Pharmacy University of Ljubljana  Ljubljana Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ma\u0161a","family":"Vidmar\u00a0Golja","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Faculty of Pharmacy University of Ljubljana  Ljubljana Slovenia"},{"name":"Department of Obstetrics and Gynaecology University Medical Centre Ljubljana  Ljubljana Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tina","family":"Kek","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology University Medical Centre Ljubljana  Ljubljana Slovenia"},{"name":"Faculty of Medicine University of Ljubljana  Ljubljana Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreja","family":"Eberlinc","sequence":"additional","affiliation":[{"name":"Department of Maxillofacial and Oral Surgery University Medical Center Ljubljana  Ljubljana Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Borut","family":"Ger\u0161ak","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Ljubljana  Ljubljana Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uro\u0161","family":"Mazi\u010d","sequence":"additional","affiliation":[{"name":"University Children's Hospital University Medical Centre Ljubljana  Ljubljana Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irena","family":"Mlinari\u010d\u2010Ra\u0161\u010dan","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Faculty of Pharmacy University of Ljubljana  Ljubljana Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ksenija","family":"Ger\u0161ak","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology University Medical Centre Ljubljana  Ljubljana Slovenia"},{"name":"Faculty of Medicine University of Ljubljana  Ljubljana 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