{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:45:38Z","timestamp":1791978338351,"version":"4.4.0"},"reference-count":63,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2017,9,26]],"date-time":"2017-09-26T00:00:00Z","timestamp":1506384000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5RO1HD073434\u201002"],"award-info":[{"award-number":["5RO1HD073434\u201002"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:sec><jats:label\/><jats:p>The molecular mechanisms linking folate deficiency and neural tube defect (NTD) risk in offspring remain unclear. Folate transporters (SLC19A1, SLC46A1, SLC25A32, and FOLH1) and folate receptors (FOLR1, FOLR2, and FOLR3) are suggested to play essential roles in transporting folate from maternal intestinal lumen to the developing embryo. Loss of function variants in these genes may affect folate availability and contribute to NTD risk. This study examines whether variants within the folate transporter and receptor genes are associated with an increased risk for myelomeningocele (MM). Exons and their flanking intron sequences of 348 MM subjects were sequenced using the Sanger sequencing method and\/or next generation sequencing to identify variants. Frequencies of alleles of single nucleotide polymorphisms (SNPs) in MM subjects were compared to those from ethnically matched reference populations to evaluate alleles\u2019 associated risk for MM. We identified eight novel variants in <jats:italic>SLC19A1<\/jats:italic> and twelve novel variants in <jats:italic>FOLR1<\/jats:italic>, <jats:italic>FOLR2<\/jats:italic>, and <jats:italic>FOLR3<\/jats:italic>. Pathogenic variants include c.1265delG in <jats:italic>SLC19A1<\/jats:italic> resulting in an early stop codon, four large insertion deletion variants in <jats:italic>FOLR3<\/jats:italic>, and a stop_gain variant in <jats:italic>FOLR3<\/jats:italic>. No new variants were identified in <jats:italic>SLC46A1<\/jats:italic>, <jats:italic>SLC25A32<\/jats:italic>, or <jats:italic>FOLH1<\/jats:italic>. In <jats:italic>SLC19A1<\/jats:italic>, c.80A&gt;G (rs1051266) was not associated with our MM cohort; we did observe a variant allele G frequency of 61.7%, higher than previously reported in other NTD populations. In conclusion, we discovered novel loss of function variants in genes involved in folate transport in MM subjects. Our results support the growing evidence of associations between genes involved in folate transport and susceptibility to NTDs.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38472","type":"journal-article","created":{"date-parts":[[2017,9,26]],"date-time":"2017-09-26T05:10:57Z","timestamp":1506402657000},"page":"2973-2984","source":"Crossref","is-referenced-by-count":29,"title":["Mutations in folate transporter genes and risk for human myelomeningocele"],"prefix":"10.1002","volume":"173","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2766-4654","authenticated-orcid":false,"given":"Tina O.","family":"Findley","sequence":"first","affiliation":[{"name":"Division of Neonatology The University of Texas Health Science Center at Houston Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joy C.","family":"Tenpenny","sequence":"additional","affiliation":[{"name":"Division of Neonatology The University of Texas Health Science Center at Houston Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle R.","family":"O'Byrne","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, McGovern Medical School The University of Texas Health Science Center at Houston Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alanna C.","family":"Morrison","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health The University of Texas Health Science Center at Houston Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Hixson","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health The University of Texas Health Science Center at Houston Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hope","family":"Northrup","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, McGovern Medical School The University of Texas Health Science Center at Houston Houston Texas"},{"name":"Shriners Hospital for Children Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2694-5833","authenticated-orcid":false,"given":"Kit Sing","family":"Au","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, McGovern Medical School The University of Texas Health Science Center at Houston Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,9,26]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2011.11.021"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23100"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.22884"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/85.2.598S"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20499"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddrr.93"},{"key":"e_1_2_6_8_1","article-title":"Genetic mechanisms of folate deficiency and neural tube defects \u2013 leaving no stone unturned","author":"Au K. 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