Journal article
Analysis of select folate pathway genes, PAX3, and human T in a midwestern neural tube defect population
Teratology (Philadelphia), Vol.59(5), pp.331-341
05/1999
DOI: 10.1002/(SICI)1096-9926(199905)59:5<331::AID-TERA4>3.0.CO;2-L
PMID: 10332959
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.
Details
- Title: Subtitle
- Analysis of select folate pathway genes, PAX3, and human T in a midwestern neural tube defect population
- Creators
- Dimitri TrembathAndrea L SherbondyDon C VandykeGary M ShawKaren TodoroffEdward J LammerRichard H FinnellStephen MarkerGary LernerJeffrey C Murray
- Resource Type
- Journal article
- Publication Details
- Teratology (Philadelphia), Vol.59(5), pp.331-341
- DOI
- 10.1002/(SICI)1096-9926(199905)59:5<331::AID-TERA4>3.0.CO;2-L
- PMID
- 10332959
- NLM abbreviation
- Teratology
- ISSN
- 0040-3709
- eISSN
- 1096-9926
- Publisher
- John Wiley & Sons, Inc; New York
- Number of pages
- 11
- Grant note
- U.S. National Institutes of Health (DE08559) U.S. Centers for Disease Control and Prevention (CCU7132238)
- Language
- English
- Date published
- 05/1999
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Developmental and Behavioral Pediatrics; Dental Research
- Record Identifier
- 9984025413102771
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