Principal investigator: James L. Mills, M.D., M.S.
The Birth Defects Research Group is a multi-center, multidisciplinary group led by NICHD to investigate the etiology of birth defects, particularly neural tube defects (NTDs). The collaborating institutions are NICHD, the National Human Genome Research Institute, the Health Research Board of Ireland, and the Department of Biochemistry, Trinity College, Dublin. This group has discovered several important factors related to NTDs, including the discovery of the first folate-related gene associated with NTDs--Methylenetetrahydrofolate reductase--and the first maternal gene--Methylenetetrahydrofolate dehydrogenase. The group was also the first to show that maternal levels of homocysteine were elevated during pregnancy for women carrying affected fetuses. The group is currently looking for other gene associations in the NTD population and expanding its investigation to include the role of folate-related enzyme genes in oral clefts.  Research studies within this topic area include:

• Genetic Risk Factors for NTDs
• Effects of Folic Acid Fortification on Twin Gestation Rates
• Investigation of the Biochemical Consequences in Pregnant Women of a Common Genetic Variant Associated with Vitamin B12 Status
• Angiogenic Factors and Placental Abruption
• The MTHFD1 R653Q Polymorphism is a Maternal Genetic Risk Factor for Severe Abruptio Placentae

Parle-McDermott A, Pangilinan F, Mills JL, Kirke PN, Gibney ER, Troendle J, O’Leary VB, Molloy AM, Conley M, Scott JM, & Brody LC. (2007). The 19-bp deletion polymorphism in intron-1 of dihydrofolate reductase (DHFR) may decrease rather than increase risk for spina bifida in the Irish population.  Am J Med Genet A, 143(11):1174-1180. [Abstract]

Parle-McDermott A, Mills JL, Molloy AM, Carroll N, Kirke PN, Cox C, Conley MR, Pangilinan FJ, Brody LC, & Scott JM. (2006). The MTHFR 1298CC and 677TT genotypes have opposite associations with red cell folate levels. Mol Genet Metab, 88(3):290-294. [Abstract]

Parle-McDermott A, Kirke PN, Mills JL, Molloy AM, Cox C, O'Leary VB, Pangilinan F, Conley M, Cleary L, Brody LC, & Scott JM. (2006). Confirmation of the R653Q polymorphism of the trifunctional C1-synthase enzyme as a maternal risk for neural tube defects in the Irish population. Eur J Hum Genet, 14(6):768-772. [Abstract]

O'Leary VB, Pangilinan F, Cox C, Parle-McDermott A, Conley M, Molloy AM, Kirke PN, Mills JL, Brody LC, Scott JM, & Members of the Birth Defects Research Group. (2006).Reduced folate carrier polymorphisms and neural tube defect risk. Mol Genet Metab, 87(4):364-369. [Abstract]

Molloy AM, Mills JL, Cox C, Daly SF, Conley M, Brody LC, Kirke PN, Scott JM, & Ueland PM. (2005). Choline and homocysteine interrelations in umbilical cord and maternal plasma at delivery. Am J Clin Nutr, 82(4):836-842. [Abstract]

O'Leary VB, Mills JL, Parle-McDermott A, Pangilinan F, Molloy AM, Cox C, Weiler A, Conley M, Kirke PN, Scott JM, & Brody LC, Birth Defects Research Group. (2005). Screening for new MTHFR polymorphisms and NTD risk. Am J Med Genet A, 138(2):99-106. [Abstract]

Parle-McDermott A, Pangilinan F, Mills JL, Signore CC, Molloy AM, Cotter A, Conley M, Cox C, Kirke PN, Scott JM, & Brody LC. (2005). A polymorphism in the MTHFD1 gene increases a mother's risk of having an unexplained second trimester pregnancy loss. Mol Hum Reprod, 11(7):477-480. [Abstract]

O'Leary VB, Mills JL, Pangilinan F, Kirke PN, Cox C, Conley M, Weiler A, Peng K, Shane B, Scott JM, Parle-McDermott A, Molloy AM, Brody LC, & Members of the Birth Defects Research Group. (2005). Analysis of methionine synthase reductase polymorphisms for neural tube defects risk association. Mol Genet Metab, 85(3):220-227. [Abstract]

Swanson DA, Pangilinan F, Mills JL, Kirke PN, Conley M, Weiler A, Frey T, Parle-McDermott A, O'Leary VB, Seltzer RR, Moynihan KA, Molloy AM, Burke H, Scott JM, & Brody LC. (2005). Evaluation of transcobalamin II polymorphisms as neural tube defect risk factors in an Irish population. Birth Defects Res A Clin Mol Teratol, 73(4):239-244. [Abstract]

Parle-McDermott A, Mills JL, Kirke PN, Cox C, Signore CC, Kirke S, Molloy AM, O'Leary VB, Pangilinan FJ, O'Herlihy C, Brody LC, & Scott JM. (2005). MTHFD1 R653Q polymorphism is a maternal genetic risk factor for severe abruptio placentae. Am J Med Genet A, 132(4):365-368. [Abstract]

Mills JL & Signore C. (2004). Neural tube defect rates before and after food fortification with folic acid. Birth Defects Res A Clin Mol Teratol, 70(11):844-845. [Abstract]

Kirke PN, Mills JL, Molloy AM, Brody LC, O'Leary VB, Daly L, Murray S, Conley M, Mayne P, Smith O, & Scott JM. (2004). Impact of the MTHFR C677T polymorphism on risk of neural tube defects: Case-control study. Brit Med J, 328:1535-1536. [Abstract]

Parle-Mc Dermott A, Mc Manus EJ, Mills JL, O'Leary VB, Pangilinan F, Cox C, Weiler A, Molloy AM, Conley M, Watson D, Scott JM, Brody LC, Kirke PN, & Members of the Birth Defects Research Group. (2003). Polymorphisms within the vitamin B12 dependent methylmalonyl-coA mutase are not risk factors for neural tube defects. Mol Genet Metabol, 80:463-468. [Abstract]

O'Leary VB, Mills JL, Kirke PN, Parle-McDermott AP, Swanson DA, Weiler A, Pangilinan F, Conley M, Molloy AM, Lynch M, Cox C, Scott JM, & Brody LC. (2003). Analysis of the human folate receptor beta gene for an association with neural tube defects. Mol Genet Metabol, 79:129-133. [Abstract]

Parle-McDermott A, Mills JL, Kirke PN, O'Leary PB, Swanson DA, Pangilanin F, Conley M, Molloy AM, Cox C, Scott JM, & Brody LC. (2003). Analysis of the MTHFR 1298 A->C and 677C->T polymorphisms as risk factors for neural tube defects. J Hum Genet, 48:190-193. [Abstract]

Birth Defects Research group (in alphabetical order): Brody LC, Conley M, Cox C, Kirke PN, McKeever MP, Mills JL, Molloy AM, O'Leary VB, Parle-McDermott A, Scott JM, & Swanson DA. (2002). A polymorphism, R653Q, in the trifunctional enzyme methylenetetrahydrofolate dehydrogenase, methenyltetrahydrofolate-cyclohydrolase, formyltetrahydrofolate synthetase (MTHFD1) is a maternal genetic risk factor for neural tube defects. Am J Hum Genet, 71:1207-1215. [Abstract]

Daly S, Mills JL, Molloy AM, Conley M, McPartlin J, Lee YJ, Young PB, Kirke PN, Weir DG, & Scott JM. (2002). Low dose folic acid lowers plasma homocysteine levels in women of child bearing age: A double blind, randomized placebo controlled trial. Q J Med, 95:733-740. [Abstract]

Molloy AM, Mills JL, McPartlin J, Kirke PN, Scott JM, & Daly S. (2002). Maternal and fetal plasma homocysteine concentrations at birth: The influence of folate, vitamin B12, and the 5,10 methylenetetrahydrofolate reductase 677 C->T variant. Am J Obstet Gynecol, 186:499-503. [Abstract]

O'Leary VB, Parle-McDermott A, Molloy AM, Kirke PN, Johnson Z, Conley M, Scott JM, & Mills JL. (2002). MTRR and MTHFR polymorphism: Link to Down syndrome? Am J Med Genet, 107:151-155. [Abstract]

Shields DC, Ramsbottom D, Donoghue C, Pinjon E, Kirke PN, Molloy AM, Edwards YH, Mills JL, Mynett-Johnson L, Weir DG, Scott JM, & Whitehead AS. (2000). Association between historically high frequencies of neural tube defects and the human T homologue of mouse T (Brachyury). Am J Med Genet, 92:206-211. [Abstract]

Molloy AM, Mills JL, Kirke PN, Weir DG, & Scott JM. (1999). Folate status and neural tube defects. Biofactors, 10(2-3):291-294. [Abstract]

Daly SF, Molloy AM, Mills JL, Lee YJ, Conley M, Kirke PN, Weir DG, & Scott JM. (1999). The influence of 5,10 methylenetetrahydrofolate reductase genotypes on enzyme activity in placental tissue. Br J Obstet Gynaecol, 106(11):1214-1218. [Abstract]