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Analysis of select folate pathway genes, PAX3, and human T in a midwestern neural tube defect population

1999; Wiley; Volume: 59; Issue: 5 Linguagem: Inglês

10.1002/(sici)1096-9926(199905)59

2472-1727

Dimitri G. Trembath, Andrea L. Sherbondy, Don C. Vandyke, Gary M. Shaw, Karen Todoroff, Edward J. Lammer, Richard H. Finnell, Stephen Marker, Gary Lerner, Jeffrey C. Murray,

Congenital Anomalies and Fetal Surgery

TeratologyVolume 59, Issue 5 p. 331-341 Original Article Analysis of select folate pathway genes, PAX3, and human T in a midwestern neural tube defect population Dimitri Trembath, Dimitri Trembath Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242–1083Search for more papers by this authorAndrea L. Sherbondy, Andrea L. Sherbondy Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242–1083Search for more papers by this authorDon C. Vandyke, Don C. Vandyke Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242–1083Search for more papers by this authorGary M. Shaw, Gary M. Shaw March of Dimes Birth Defects Foundation, California Birth Defects Monitoring Program, Emeryville, California 94608Search for more papers by this authorKaren Todoroff, Karen Todoroff March of Dimes Birth Defects Foundation, California Birth Defects Monitoring Program, Emeryville, California 94608Search for more papers by this authorEdward J. Lammer, Edward J. Lammer Division of Medical Genetics, Children's Hospital of Oakland, Oakland, California 94609–1809Search for more papers by this authorRichard H. Finnell, Richard H. Finnell Department of Veterinary Anatomy and Public Health, College of Veterinary Medicine, Texas A&M University, College Station, Texas 77843–4458Search for more papers by this authorStephen Marker, Stephen Marker Minneapolis Spina Bifida Clinic, Park Nicollet Medical Center, Minneapolis, Minnesota 55404Search for more papers by this authorGary Lerner, Gary Lerner Children's Hospital, Omaha, Nebraska 68114Search for more papers by this authorJeffrey C. Murray, Corresponding Author Jeffrey C. Murray jeff-murray@uiowa.edu Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242–1083 Department of Biological Sciences, University of Iowa, Iowa City, Iowa 52242–1324Department of Pediatrics, University of Iowa, 200 Hawkins Drive, W229–1 GH, Iowa City, IA 52242–1083.Search for more papers by this author Dimitri Trembath, Dimitri Trembath Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242–1083Search for more papers by this authorAndrea L. Sherbondy, Andrea L. Sherbondy Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242–1083Search for more papers by this authorDon C. Vandyke, Don C. Vandyke Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242–1083Search for more papers by this authorGary M. Shaw, Gary M. Shaw March of Dimes Birth Defects Foundation, California Birth Defects Monitoring Program, Emeryville, California 94608Search for more papers by this authorKaren Todoroff, Karen Todoroff March of Dimes Birth Defects Foundation, California Birth Defects Monitoring Program, Emeryville, California 94608Search for more papers by this authorEdward J. Lammer, Edward J. Lammer Division of Medical Genetics, Children's Hospital of Oakland, Oakland, California 94609–1809Search for more papers by this authorRichard H. Finnell, Richard H. Finnell Department of Veterinary Anatomy and Public Health, College of Veterinary Medicine, Texas A&M University, College Station, Texas 77843–4458Search for more papers by this authorStephen Marker, Stephen Marker Minneapolis Spina Bifida Clinic, Park Nicollet Medical Center, Minneapolis, Minnesota 55404Search for more papers by this authorGary Lerner, Gary Lerner Children's Hospital, Omaha, Nebraska 68114Search for more papers by this authorJeffrey C. Murray, Corresponding Author Jeffrey C. Murray jeff-murray@uiowa.edu Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242–1083 Department of Biological Sciences, University of Iowa, Iowa City, Iowa 52242–1324Department of Pediatrics, University of Iowa, 200 Hawkins Drive, W229–1 GH, Iowa City, IA 52242–1083.Search for more papers by this author First published: 14 May 1999 https://doi.org/10.1002/(SICI)1096-9926(199905)59:5 3.0.CO;2-LCitations: 76AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Neural tube defects (NTDs) are a common birth defect, seen in approximately 1/1,000 births in the United States. NTDs are considered a complex trait where several genes, interacting with environmental factors, create the phenotype. Using a Midwestern NTD population consisting of probands, parents, and siblings from Iowa, Minnesota, and Nebraska, we analyzed a range of candidate genes, including 5,10–methylenetetrahydrofolate reductase (MTHFR), folate receptors-α (FOLR1; hereafter abbreviated “FR-α”) and -β (FOLR2; hereafter, “FR-β”), methionine synthase (hereinafter, “MS”), T, the human homolog of the murine Brachyury gene, and the paired-box homeotic gene 3 (PAX3), for association with NTDs. We were unable to demonstrate an association using a previously described Ala→Val mutation in MTHFR and the majority of our NTD populations. However, we discovered a silent polymorphism in exon 6 of MTHFR which conserved a serine residue and which showed significant association with NTDs in our Iowa population. Analysis of exon 7 of MTHFR then demonstrated an Ala→Glu mutation which was signficantly associated with our Iowa NTD population; however, we could not replicate this result either in a combined Minnesota/Nebraska or in a California NTD population. Using polymorphic markers for MS, FR-β, T, and PAX3, we were unable to demonstrate linkage disequilibrium with our NTD populations. A mutation search of FR-α revealed one proband with a de novo silent mutation of the stop codon. This work provides a new panel of genetic variants for studies of folate metabolism and supports, in some NTD populations, an association between MTHFR and NTDs. Teratology 59:331–341, 1999. © 1999 Wiley-Liss, Inc. Citing Literature Volume59, Issue5May 1999Pages 331-341 RelatedInformation