Folate administration substantially reduces the risk on neural tube defects (NTD). The interest for studying a disturbed homocysteine (Hcy) metabolism in relation to NTD was raised by the observation of elevated blood Hcy levels in mothers of a NTD child. This observation resulted in the examination of enzymes involved in the folate-dependent Hcy metabolism. Thus far, this has led to the identification of the first and likely a second genetic risk factor for NTD. The C677T and A1298C mutations in the methylenetetrahydrofolate reductase (MTHFR) gene are associated with an increased risk of NTD and cause elevated Hcy concentrations. These levels can be normalized by additional folate intake. Thus, a dysfunctional MTHFR partly explains the observed elevated Hcy levels in women with NTD pregnancies and also, in part, the protective effect of folate on NTD. Although the MTHFR polymorphisms are only moderate risk factors, population-wide they may account for an important part of the observed NTD prevalence.
KarfunkelP.The mechanism of neural tube formation. Int Rev Cytol38:245–271, 1974.
2.
CoppAJ, BrookFA, EstibeiroJP, ShumASW, CockroftDL. The embryonic development of mammalian neural tube defects. Prog Neurobiol35:363–403, 1990.
3.
SchoenwolfGC, SmithJL. Mechanisms of neurulation: Traditional viewpoint and recent advances. Development109:243–270, 1990.
4.
SmithJL, SchoenwolfGC. Neurulation: Coming to closure. Trends Neurosci20:510–517, 1997.
5.
NieuwkoopPD. The neural induction process: Its morphogenetic aspects. Int J Dev Biol 43SI:615–623, 1999.
6.
BachillerD, KlingensmithJ, KempC, BeloJA, AndersonRM, MaySR, McMahonJA, McMahonAP, HarlandRM, RossantJ, De RobertisEM. The organizer factors Chordin and Noggin are required for mouse forebrain development. Nature403:658–661, 2000.
7.
JacobsonAG, GordonR.Changes in the shape of the developing vertebrate nervous system analyzed experimentally, mathematically and by computer simulation. J Exp Zool197:191–246, 1976.
8.
SchoenwolfGC. Cell movements driving neurulation in avian embryos. Development2:(Suppl)157–168, 1991.
9.
Van StraatenHW, HekkingJW, Wiertz HoesselsEJ, ThorsF, DrukkerJ.Effect of the notochord on the differentiation of a floor plate area in the neural tube of the chick embryo. Anat Embryol Berl177:317–324, 1988.
10.
SmithJL, SchoenwolfGC. Notochordal induction of cell wedging in the chick neural plate and its role in neural tube formation. J Exp Zool250:49–62, 1989.
11.
PlaczekM, DoddJ, JessellTM. The case for floor plate induction by the notochord. Curr Opin Neurobiol10:15–22, 2000.
12.
SchoenwolfGC, FranksMV. Quantitative analyses of changes in cell shapes during bending of the avian neural plate. Dev Biol105:257–272, 1984.
13.
JacobsonAG. Some forces that shape the nervous system. Zoon6:13–21, 1978.
14.
NageleRG, HunterE, BushK, LeeHY. Studies on the mechanisms of neurulation in the chick: Morphometric analysis of force distribution within the neuroepithelium during neural tube formation. J Exp Zool244:425–436, 1987.
15.
SchoenwolfGC, FolsomD, MoeA.A reexamination of the role of microfilaments in neurulation in the chick embryo. Anat Rec220:87–102, 1988.
16.
FerreiraMC, HilferSR. Calcium regulation of neural fold formation: Visualization of the actin cytoskeleton in living chick embryos. Dev Biol159:427–440, 1993.
17.
HildebrandJD, SorianoP.Shroom, a PDZ domain-containing actin-binding protein, is required for neural tube morphogenesis in mice. Cell99:485–497, 1999.
18.
HildebrandJD, SorianoP.Shroom, a PDZ domain-containing actin-binding protein, is required for neural tube morphogenesis in mice. Cell99:485–497, 1999.
19.
Van StraatenHWM, JanssenHCJP, PeetersMCE, CoppAJ, HekkingJWM. Neural tube closure in the chick embryo is multiphasic. Dev Dynamics207:309–318, 1996.
20.
AlvarezIS, SchoenwolfGC. Expansion of surface epithelium provides the major extrinsic force for bending of the neural plate. J Exp Zool261:340–348, 1992.
21.
HackettDA, SmithJL, SchoenwolfGC. Epidermal ectoderm is required for full elevation and for convergence during bending of the avian neural plate. Dev Dynamics210:397–406, 1997.
22.
Van StraatenHWM, PeetersMCE, SzpakKWF, HekkingJWM. Initial closure of the mesencephalic neural groove in the chick embryo involves a releasing zipping-up mechanism. Dev Dynamics209:333–341, 1997.
23.
GoldenJA, ChernoffGF. Anterior neural tube closure in the mouse: Fuel for disagreement with the classical theory. Clin Res31:127a, 1983.
24.
GoldenJA, ChernoffGF. Intermittent pattern of neural tube closure in two strains of mice. Teratology47:73–80, 1993.
25.
PeetersMCE, ViebahnC, HekkingJWM, Van StraatenHWM. Neurulation in the rabbit embryo. Anat Embryol197:167–175, 1998.
26.
O'RahillyR. Müller. Bidirectional closure of the rostral neuropore in the human embryo. Am J Anat184:259–268, 1989.
27.
SellerMJ. Multi-site neural tube closure in humans and maternal folate supplementation. Am J Med Genet58:222–224, 1995.
28.
TamPP. A study of the pattern of prospective somites in the presomitic mesoderm of mouse embryos. J Embryol Exp Morphol92:269–285, 1986.
29.
MüllerF, O'RahillyR.The development of the human brain, the closure of the caudal neuropore, and the beginning of the secondary neurulation at stage 12. Anat Embryol176:413–430, 1987.
30.
CoppAJ, BrookFA. Does lumbosacral spina bifida arise by failure of neural folding or by defective canalization?J Med Genet26:160–166, 1989.
31.
GriffithCM, WileyMJ, SandersEJ. The vertebrate tail bud: three germ layers from one tissue. Anat Embryol185:101–113, 1992.
32.
SchoenwolfGC. Histological and ultrastructural studies of secondary neurulation in mouse embryos. Am J Anat169:361–376, 1984.
33.
O'RahillyR. Müller. Neurulation in the normal human embryo. Ciba Found Symp181:70–82, 1994.
34.
LemireRJ, LoeserJD, LeechRW, AlvordEC. Normal and Abnormal Development of the Human Nervous System. Hagerstown, MD: Harper & Row, 1975.
35.
CatalaM, TeilletMA, LedouarinNM. Organization and development of the tail bud analyzed with the quail-chick chimaera system. Mech Dev51:51–65, 1995.
36.
MatsonD.Neurosurgery of Infancy and Childhood. Springfield, IL, Charles C. Thomas, 1969.
37.
LarrocheJ-C. Malformations of the nervous system. In: AdamsJH, CorsellisJAN, DuchenLW, Eds. Greenfield's Neuropathology. New York: Wiley & Sons, p385, 1984.
38.
LemireRJ, SiebertJR. Anencephaly: Its spectrum and relationship to neural tube defects. J Craniofac Genet Dev Biol10:163–174, 1990.
39.
NakanoRK. Anencephaly: A review. Dev Med Child Neurol15:383–400, 1973.
40.
MelnickM, MyrianthopoulosNC. Studies in neural tube defects. II. Pathological findings in a prospectively collected series of anencephalics. Am J Med Genet26:797–810, 1987.
41.
YenIH, KhouryMJ, EricksonJD, JamesLM, WatersGD, BerryRJ. The changing epidemiology of neural tube defects: United States, 1968–1989. Am J Dis Child146:857–861, 1992.
42.
IngrahamFD, ScottHW. Arnold-Chiari malformations. N Engl J Med229:108, 1943.
43.
MealeyJJr., DzenitisAJ, HockeyAA. The prognosis of encephaloceles. J Neurosurg32:209–218, 1970.
44.
BrownMS, Sheridan-PerieraM.Outlook for the child with an encephalocele. Pediatrics90:914–919, 1992.
45.
FriedeRL. Developmental Neuropathology. New York: Springer-Verlag, 1989.
46.
CurnesJT, OakesWJ. Parietal cephaloceles: Radiographic and magnetic resonance imaging evaluation. Pediatr Neurosci14:71–76, 1988.
47.
Von BrandenskyG, KlickA.Encephalocele und hydrocephalus. Z Kinderchir7:583, 1969.
48.
CastilloM, QuencerRM, DominguezR.Chiari III malformations: Imaging features. Am J Neuroradiol13:107–113, 1992.
49.
DolkH, DewalsP, GillerotY, LechatMF, AymeS, CornelM, CuschieriA, GameE, GoujardJ, LaurenceKM, LillisD, LysF.Heterogeneity of neural tube defects in Europe: The significance of site of defect and presence of other major anomalies in relation to geographic differences in prevalence. Teratology44:547–559, 1991.
50.
ShiotaK.Teratothanasia: Prenatal loss of abnormal conceptuses and the prevalence of various malformations during human gestation. Birth Defects29:189–199, 1993.
51.
MyrianthopoulosNC, MelnickM.Studies in neural tube defects. I. Epidemiologic and etiologic aspects. Am J Med Genet26:783–796, 1987.
52.
LemireRJ. Neural tube defects. J Am Med Assoc259:558–562, 1988.
53.
StoneDH. The declining prevalence of anencephalus and spina bifida: It's nature, causes and implications. Dev Med Child Neurol29:541–546, 1987.
ChanA, RobertsonEF, HaanEA, KeaneRJ, RanieriE, CarneyA.Prevalence of neural tube defects in South Australia, 1966–1991: Effectiveness and impact of prenatal diagnosis. Br Med J307:703–706, 1993.
56.
RobertsHE, MooreCA, CraganJD, FernhoffPM, KhouryMJ. Impact of prenatal diagnosis on the birth prevalence of neural tube defects, Atlanta, 1990-1991. Pediatrics96:880–883, 1995.
57.
JanerichDT. Epidemic waves in the prevalence of anencephaly and spina bifida in New York State. Teratology8:253–256, 1973.
58.
KirkePN, ElwoodJH. Anencephaly in the United Kingdom and Republic of Ireland. Br Med J289:1621, 1984.
59.
BrownAS, SusserES. Sex differences in prevalence of congenital neural defects after periconceptional famine exposure. Epidemiology8:55–58, 1997.
60.
HolmesLB. Driscoll SG, Atkins L. Etiologic heterogeneity of neural-tube defects. N Eng J Med294:365–369, 1976.
61.
CarterCO. Clues to the aetiology of neural tube malformations. Dev Med Child Neurol16(suppl 32):3–15, 1974.
62.
CarterCO, EvansK.Children of adult survivors with spina bifida cystica. Lancet2:924–926, 1973.
63.
LorberJ.The family history of spina bifida cystica. Pediatrics35:598, 1965.
64.
JanerichDT, PiperJ.Shifting genetic patterns in anencephaly and spina bifida. J Med Genet51:101–105, 1978.
65.
TorielloHV, HigginsJV. Occurrence of neural tube defects among first-, second-, and third-degree relatives of probands: Results of a United States study. Am J Med Genet15:601–606, 1983.
66.
HallJG, FriedmanJM, KennaBA, PopkinJ, JawandaM, ArnoldW.Clinical, genetic, and epidemiological factors in neural tube defects. Am J Hum Genet43:827–837, 1988.
67.
ChatkuptS, SkurnickJH, JaggiM, MitrukaK, KoenigsbergerMR, JohnsonWG. Study of genetics, epidemiology, and vitamin usage in familial spina bifida in the United States in the 1990s. Neurology44:65–70, 1994.
68.
Martínez-FríasM-L. Valproic acid and spina bifida. Lancet338:196–197, 1991.
69.
CampbellRL, DaytonDH, SohalGS. Neural tube defects: a review of human and animal studies on the etiology of neural tube defects. Teratology34:171–187, 1986.
70.
GonzalezMJ, SchmitzKJ, MatosMI, LopezD, RodriguezJR, GorrinJJ. Folate supplementation and neural tube defects: A review of a public health issue. P R Health Sci J16:387–393, 1997.
71.
ShawGM, TodoroffK, VelieEM, LammerEJ. Maternal illness, including fever and medication use as risk factors for neural tube defects. Teratology57:1–7, 1998.
72.
MacMahonB, YenS.Unrecognised epidemic of anencephaly and spina bifida. Lancet1:31–33, 1971.
73.
SteinZ, SusserM, SaenperG, MarollaF.Famine and Human Development: The Dutch Hunger Winter of 1944-1945. New York: Oxford University Press, 1975.
74.
MichieCA. Neural tube defects in 18th century. Lancet337:504, 1991.
75.
SteinSC, FeldmanJG, FriedlanderM, KleinRJ. Is myelomeningocele a disappearing disease?Pediatrics69:511–514, 1982.
76.
HibbardBM. The role of folic acid in pregnancy: With particular reference to anaemia, abruption and abortion. J Obstet Gynaecol Br Commonwlth71:529–542, 1964.
77.
HibbardED, SmithellsRW. Folic acid metabolism and human embryopathy. Lancet1:1254, 1965.
HoffbrandAV, NewcombeBF, MollinDL. Method of assay of red cell folate activity and the value of the assay as a test for folate deficiency. J Clin Pathol19:17–28, 1966.
80.
SmithellsRW, SheppardS, SchorahCJ, SellerMJ, NevinNC, HarrisR, ReadAP, FieldingDW. Possible prevention of neural-tube defects by periconceptional vitamin supplementation. Lancet1:339–340, 1980.
81.
LaurenceKM, JamesN, MillerMH, CampbellH.Increased risk of recurrence of neural tube defects to mothers on a poor diet and possible benefits of dietary counseling. Br Med J281:1542–1594, 1980.
SellerMJ. Risk in Spina Bifida. Dev Med Child Neurol36:1021–1025, 1994.
84.
LaurenceKM, JamesN, MillerMH, TennantGB. Campbell H. Double-blind randomised control trial of folate treatment before conception to prevent recurrence of neural-tube defects. Br Med J282:1509–1511, 1981.
85.
ElwoodJM. Can vitamins prevent neural tube defects?Can Med Assoc J129:1088–1092, 1983.
86.
WaldNJ, PolaniPE. Neural-tube defects and vitamins: The need for a randomized clinical trial. Br J Obstet Gynaecol91:516–523, 1984.
NevinNC, SellerMJ. Prevention of neural-tube defect recurrences. Lancet1:178–179, 1990.
92.
VergelRG, SanchezLR, HerederoBL, RodriguezPL, MartinezAJ. Primary prevention of neural tube defects with folic acid supplementation: Cuban experience. Prenat Diagn10:149–152, 1990.
93.
MRC Vitamin Study Research Group.Prevention of neural-tube defects: Results of the Medical Research Council vitamin study. Lancet338:131–137, 1991.
94.
CzeizelAE, DudasI.Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med327:1832–1835, 1992.
95.
MulinareJ, CorderoJF, EricksonJD, BerryRJ. Periconceptional use of multivitamins and the occurrence of neural tube defects. J Am Med Assoc260:3141–3145, 1988.
96.
MillunskyA, JickH, JickSS, BruelCL, MacLaughlinDS, RothmanKJ, WillettW.Multivitamin/folic acid supplementation in early pregnancy reduces the prevalence of neural tube defects. J Am Med Assoc262:2847–2852, 1989.
97.
WerlerMM, ShapiroS, MitchellAA. Periconceptional folic acid exposure and risk of occurrence neural tube defects. J Am Med Assoc269:1257–1261, 1993.
98.
ShawGM, SchafferD, VelieEM, MorlandKM, HarrisJA. Periconceptional vitamin use, dietary folate, and the occurrence of neural tube defects. Epidemiology6:219–226, 1995.
99.
BowerC, StanleyFJ. Dietary folate as a risk factor for neural tube defects, evidence from a case-control study in Western Australia. Med J Aust150:613–619, 1989.
100.
BerryRJ, LiZ, EricksonJD, LiS, MooreCA, WangH, MulinareJ, ZhaoP, WongL-YC, GindlerJ, HongS-X, CorreaA.Prevention of neural-tube defects with folic acid in China. N Engl J Med341:1485–1490, 1999.
101.
MillsJL, RhoadsGG, SimpsonJL, CunninghamGC, ConleyMR, LassmanMR, WaldenME, DeppOR, HoffmannHJ. The absence of a relation between the periconceptional use of vitamins and neural-tube defects. N Engl J Med321:430–435, 1989.
102.
ScottJM, WeirDG, KirkePN. Folate and neural tube defects. In: BaileyL, Ed. Folate in Health and Disease. New York: Marcel Dekker, pp 329–360, 1995.
103.
SchaapveldK, HirasingEA. Recente ontwikkelingen in de preventieve gezondheidszorg. Ned T Geneesk141:1909–1912, 1997.
104.
De BreeA, Van DusseldorpM, BrouwerIA, Van het HofKH, Steegers-TheunissenRMP. Folate intake in Europe: Recommended, actual and desired intake. Eur J Clin Nutr51:643–660, 1997.
105.
McNultyH, CuskellyGJ, WardM.Response of red blood cell folate to intervention: Implications for folate recommendations for the prevention of neural tube defects. Am J Clin Nutr71:1308S–1311S, 2000.
106.
PasternackLB, LittlepageLE, LaudeDAJr., ApplingDR. 13C NMR analysis of the use of alternative donors to the tetrahydrofolate-dependent one-carbon pools in Saccharomyces cerevisiae.Arch Biochem Biophys326:158–165, 1996.
107.
ShaneB.Folylpolyglutamate synthesis and role in the regulation of one-carbon metabolism. Vitam Horm45:263–335, 1989.
108.
ApplingDR. Compartimentation of folate-mediated one carbon metabolism in eukaryotes. FASEB J5:2645–2651, 1991.
109.
KastanosEK, WoldmanYY, ApplingDR. Role of mitochondrial and cytoplasmic serine hydroxymethyltransferase isozymes in de novo purine synthesis in Saccharomyces cerevisiae.Biochemistry36:14956–14964, 1997.
110.
ShaneB, StokstadELR. Folates in the synthesis and catabolism of histidine. In: BlakleyRL, BenkovicSJ, Eds. Folates and Pterins, Vol 1. New York: Wiley & Sons, pp 433–456, 1984.
111.
KrebsHA, HemsR, TylerB.The regulation of folate and methionine metabolism. Biochemistry158:341–353, 1976.
112.
SmithGK, BenkovicPA, BenkovicSJ. L-(–)10-formyltetrahydrofolate is the cofactor for glycinamide ribonucleotide transformylase from chicken liver. Biochemistry20:4034–4036, 1981.
113.
TanLU, DruryEJ, MackenzieRE. Methylenetetrahydrofolate dehydrogenase-methenyl-tetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase: A multifunctional protein from porcine liver. J Biol Chem252:1117–1122, 1977.
114.
HalstedCH. Intestinal absorption and malabsorption of folates. Annu Rev Med31:79–87, 1980.
115.
RosenbergIH. Folate absorption and transport. In: CooperBA, WhiteheadVM. Eds. Chemistry and Biology of Pteridines: Pteridines and Folic Acid Derivatives. Berlin, de Gruyter, p587, 1986.
116.
SelhubJ, EmmanouelD, StavropoulosT, ArnoldR.Renal folate absorption and the kidney folate binding protein. I. Urinary clearance studies. Am J Physiol252:F750–F756, 1987.
117.
ShaneB, StokstadELR. The interrelationships among folate, vitamin B12, and methionine metabolism. Adv Nutr Res5:133–170, 1983.
118.
FanJ, VitolsKS, HuennekensFM. Multiple folate transport systems in L1210 cells. Adv Enzyme Regul32:3–15, 1992.
119.
SirotnakFM, GoutalLJ, MinesLS. Extent of the requirement for folate transport by L1210 cells for growth and leukemogenesis in vivo.Cancer Res45:3992–4000, 1985.
120.
KamenBA, CapdevilaA.Receptor-mediated folate accumulation is regulated by the cellular folate content. Proc Natl Acad SciU S A83:5983, 1986.
121.
AntonyAC. The biological chemistry of folate receptors. Blood79:2807–2820, 1992.
122.
BrigleKE, SpinellaMF, SierraEE, GoldmanID. Characterization of a mutation in the reduced folate carrier in transport defective L1210 murine leukemia cell line. J Biol Chem270:22974–22979, 1995.
123.
HendersonGB. Folate-binding proteins. Annu Rev Nutr10:319–335, 1990.
124.
KamenBA, WangMT, StreckfussAJ, PeryeaX, AndersonRGW. Delivery of folates to the cytoplasm of MA104 cells is mediated by a surface membrane receptor that recycles. J Biol Chem263:13602–13609, 1988.
125.
KamenBA, SmithAK, AndersonRGW. The folate receptor works in tandem with a Probenecid-sensitive carrier in MA104 cells in vitro.J Clin Invest87:1442, 1991.
126.
AndersonRGW, KamenBA, RothbergKG, LaceySW. Potocytosis: Sequestration and transport of small molecules by caveolae. Science255:410, 1992.
127.
SelhubJ.Folate binding proteins. Mechanism for placental and intestinal uptake. In: AllenL, KingJ, LönnerdalB, Eds. Nutrient Relation during Pregnancy, Lactation, and Infant Growth. New York: Plenum Press, pp141–149, 1994.
128.
HjelleJT, ChristensenEI, CaroneFA, SelhubJ.Cell fractionation and electron microscope studies of kidney folate-binding protein. Am J Physiol260:C338–C346, 1991.
129.
RothbergKG, YingY, KolhouseJF, KamenBA, AndersonRGW. The glycophospholipid-linked folate receptor internalizes folate without entering the clathrin-coated pit endocytic pathway. J Cell Biol110:637–649, 1990.
130.
AntonyAC. Folate receptors. Annu Rev Nutr16:501–521, 1996.
131.
RagoussisJ, SengerG, TrowsdaleJ, CampbellIG. Genomic organization of the human folate receptor genes on chromosome 11q13. Genomics14:423–430, 1992.
132.
PrasadPD, RamamoorthyS, MoeAJ, SmithCH, LeibackFH, GanapathyV.Selective expression of the high-affinity isoform of the folate receptor (FR-alpha) in the human placental syncytrophoblast and choriocarcinoma cells. Biochem Biophys Acta1223:71–75, 1994.
133.
WangH, RossJF, RatnamM.Structure and regulation of a polymorphic gene encoding folate receptor type γ/γ′. Nucleic Acids Res26:2132–2142, 1998.
134.
ShenF, RossJF, WangX, RatnamM.Identification of a novel folate receptor, a truncated receptor, and receptor type β in hematopoietic cells: cDNA cloning, expression, immunoreactivity, and tissue specificity. Biochemistry33:1209–1215, 1994.
135.
RossJF, ChaudhuriPK, RatnamM.Differential regulation of folate receptor isoforms in normal and malignant tissues in vivo and in established cell lines: Physiological and clinical implications. Cancer73:2432–2443, 1993.
136.
SchirchV.Enzymatic determinations of folate pools. Methods Enzymol281:77–81, 1997.
McGuireJJ, BertinoJR. Enzymatic synthesis and function of folylpolyglutamates. Mol Cell Biochem28:19–48, 1981.
139.
RosenblattDS. Inherited disorders of folate transport and metabolism. In: ScriverCR, BeaudetAL, SlyWS, ValleD, Eds. The Metabolic and Molecular Bases of Inherited Disease, 7th edition. New York: McGraw-Hill, pp3111–3128, 1995.
140.
LoweKE, OsborneCB, LinB-F, KimJ-S, HsuJ-C, ShaneB.Regulation of folate and one-carbon metabolism in mammalian cells. II. Effect of folylpoly-γ-glutamate synthetase substrate specificity and level on folate metabolism and folylpoly-γ-glutamate specificity of metabolic cycles of one-carbon metabolism. J Biol Chem268:21665–21673, 1993.
141.
LinB-F, HuangR-FS, ShaneB.Regulation of folate and one-carbon metabolism in mammalian cells. III. Role of mitochondrial folylpoly-γ-glutamate synthetase. J Biol Chem268:21674–21679, 1993.
142.
FreemantleSJ, TaylorSM, KrystalG, MoranRG. Upstream organization of and multiple transcripts from the human folylpoly-gammaglutamate synthetase gene. J Biol Chem270:9579–9584, 1995.
143.
ChenL, QiH, KorenbergJ, GarrowTA, ChoiY-J, ShaneB.Purification and properties of human cytosolic folylpoly-gammaglutamate synthetase and organization, localization, and differential splicing of its gene. J Biol Chem271:13077–13087, 1996.
144.
ZamierowskiMM, WagnerC.Identification of folate binding proteins in rat liver. J Biol Chem252:933–938, 1977.
145.
CybulskiRL, FisherRR. Uptake of oxidized folates by rat liver mitochondria. Biochim Biophys Acta646:329–333, 1981.
146.
LinB-F, ShaneB.Expression of Escherichia coli folylpolyglutamate synthetase in the Chinese hamster ovary cell mitochondrion. J Biol Chem269:9705–9713, 1994.
OsborneCB, LoweKE, ShaneB.Regulation of folate and one-carbon metabolism in mammalian cells. I. Folate metabolism in Chinese hamster ovary cells expressing Escherichia coli or human folylpoly-γ-glutamate synthetase activity. J Biol Chem268:21657–21664, 1993.
149.
PriestDE. Folates in tissues and cells. In: CooperBA, WhiteheadVM, Eds. Chemistry and Biology of Pteridines: Pteridines and Folic Acid Derivatives. Berlin, de Gruyter, p479, 1986.
150.
YeoE-J, WagnerC.Tissue distribution of glycine N-methyltransferase, a major folate-binding protein of liver. Proc Natl Acad Sci U S A91:210–214, 1994.
151.
MackenzieRE. Summary. Pteroylpolyglutamate metabolism. In: CooperBA, WhiteheadVM, Eds. Chemistry and Biology of Pteridines: Pteridines and Folic Acid Derivatives. Berlin, de Gruyter, p767, 1986.
152.
SikkaPK, McMartinKE. Determination of folate transport pathways in cultured rat proximal tubule cells. Chemico-Biological Interact114:15–31, 1998.
153.
KirkePN, MolloyAM, DalyLE, BurkeH, WeirDG, ScottJM. Maternal plasma folate and vitamin B12 are independent risk factors for neural tube defects. Q J Med86:703–708, 1993.
154.
DalyLE, KirkePN, MolloyA, WeirDG, ScottJM. Folate levels and neural tube defects: Implications for prevention. J Am Med Assoc274:1698–1702, 1995.
155.
ScottJM, KirkePN, WeirDG. The role of nutrition in neural tube defects. Annu Rev Nutr10:277–295, 1990.
156.
Steegers-TheunissenRPM, BoersGHJ, TrijbelsFJM, FinkelsteinJD, BlomHJ, ThomasCMG, BormGF, WoutersMGAJ, EskesTKAB. Maternal hyperhomocysteinemia: A risk factor for neural-tube defects?Metabolism43:1475–1480, 1994.
157.
MillsJL, McPartlinJM, KirkePN, LeeYJ, ConleyMR, WeirDG, ScottJM. Homocysteine metabolism in pregnancies complicated by neural-tube defects. Lancet345:149–151, 1995.
158.
Van der PutNMJ, ThomasCMG, EskesTKAB, TrijbelsFJM, Steegers-TheunissenRPM, MarimanECM, de Graaf-HessA, SmeitinkJAM, BlomHJ. Altered folate and vitamin B12 metabolism in families with spina bifida offspringQ J Med90:505–510, 1997.
159.
YatesJRW, Ferguson-SmithMA, ShenkinA, Guzman-RodriguezR, WhiteM, ClarkBJ. Is disordered folate metabolism the basis for the genetic predisposition to neural-tube defects?Clin Genet31:279–287, 1987.
160.
SchorahCJ, HabibzadehN, WildJ, SmithellsRW. Possible abnormalities of folate and vitamin B12 metabolism associated with neural-tube defects. Ann N Y Acad Sci778:81–91, 1993.
161.
WildJ, SchorahCJ, SheldonTA, SmithellsRW. Investigation of factors influencing folate status in women who have had a neural tube defect-affected infant. Br J Obstet Gynaecol100:456–459, 1993.
162.
BowerC, StanleyFJ, CroftM, DeKlerkNH. Absorption of pteroylpolyglutamates in mothers of infants with neural tube defects. Br J Nutr69:827–834, 1993.
163.
DavisBA, BaileyLB, GregoryIIIJF, TothJP, DeanJ, StevensonRE. Folic acid absorption in women with a history of pregnancy with neural tube defects. Am J Clin Nutr62:782–784, 1995.
164.
HabibzadehN, SchorahCJ, SellerMJ, SmithellsRW, LeveneMl. Uptake and utilization of DL-5-[methyl]-14C]tetrahydropteroyl-monoglutamate by cultured cytotrophoblasts associated with neural tube defects. Proc Soc Exp Biol Med203:45–54, 1993.
165.
LucockMD, WildJ, SchorahCJ, LeveneMI, HartleyR.The methylfolate axis in neural tube defects: in vitro characterisation and clinical investigation. Biochem Med Metab Biol52:101–114, 1994.
166.
LucockMD, DaskalakisI, LumbCH, SchorahCJ, LeveneMI. Impaired regeneration of monoglutamyl tetrahydrofolate leads to cellular folate depletion in mothers affected by a spina bifida pregnancy. Mol Genet Metab65:18–30, 1998.
167.
FinkelsteinJD, MartinJJ. Methionine metabolism in mammals: Adaptation to methionine excess. J Biol Chem261:1582–1587, 1986.
168.
FinkelsteinJD. Methionine metabolism in mammals. J Nutr Biochem1:228–237, 1990.
169.
AkermanK, KarkolaK, KajanderO.Methionine adenosyltransferase activity in cultured cells and in human tissues. Biochim Biophys Acta1097:140–144, 1991.
170.
ScottJM, WeirDG, MolloyA, MacPartlinJ, DalyL, KirkeP.Folic acid metabolism and mechanisms of neural tube defects. CIBA Foundation Symposium181:180–191, 1994.
171.
TaborH, RosenthalSM, TaborCW. The biosynthesis of spermidine and spermine from putrescine and methionine. J Biol Chem233:907, 1958.
172.
MuddSH, LevyHL, SkovbyF.Disorders of transsulfuration. In: ScriverCR, BeaudetAL, SlyWS, ValleD, Eds. The Metabolic Basis of Inherited Disease. 6th edition. New York: McGraw-Hill, p693, 1989.
173.
FowlerB.Disorder of homocysteine metabolism. J Inher Metab20:270–285, 1997.
174.
TaylorRT, WeissbachH.N5-Methyltetrahydrofolate-homocysteine methyltransferases. In: BoyerPD, Ed. The Enzymes, 3rd edition. New York: Academic Press, p121, 1973.
175.
McKeeverMP, WeirDG, MolloyA, ScottJM. Betainehomocysteine methyltransferase: Organ distribution in man, pig and rat and subcellular distribution in rat. Clin Sci81:551–556, 1991.
176.
AllenRH, StablerSP, LindenbaumJ.Serum betaine, N,N-dimethylglycine and N-methylglycine levels in patients with cobalamin and folate deficiency and related inborn errors of metabolism. Metabolism42:1448–1460, 1993.
177.
FinkelsteinJD, MartinJJ. Methionine metabolism in mammals: Distribution of homocysteine between competing pathways. J Biol Chem259:9508–9513, 1984.
178.
FinkelsteinJD. The regulation of homocysteine metabolism. In: GrahamI, RefsumH, RosenbergIH, UelandPM, ShumanJM, Eds. Homocysteine Metabolism: From Basic Science to Clinical Medicine. Dordrecht, The Netherlands, Kluwer Academic Publishers, p3–9, 1997.
179.
Van der MolenEF, HiipakkaMJ, VanLith-Zanders, BoersGHJ, Van den HeuvelLPWJ, MonnensLAH, BlomHJ. Homocysteine metabolism in endothelial cells of a patient homozygous for cystathionine β-synthase (CS) deficiency. Thromb Haemost78:827–833, 1997.
180.
AhiramatsuT, FukagawaNK, MarchiniJS, CortiellaJ, YuY-M. ChapmanTE, YoungVR. Methionine and cysteine kinetics at different intakes of cystine in healthy adult men. Am J Clin Nutr60:525–533, 1994.
181.
FukagawaN, YuY-M, YoungVR. Methionine and cysteine kinetics at different intakes of methionine and cystine in elderly men and women. Am J Clin Nutr68:380–388, 1998.
182.
CantoniGL, RichardsHH, ChiangPK. Inhibitors of S-adenosylhomocysteine hydrolase and their role in the regulation of biological methylation. In: UsdinE, BorchardtRT, CrevelingCR, Eds. Transmethylation. New York: Elsevier/North-Holland, p155, 1979.
183.
TaokaS, OhjaS, ShanX, KrugerWD, BanerjeeR.Evidence for heme-mediated redox regulation of human cystathionine β-synthase activity. J Biol Chem273:25179–25184, 1998.
184.
Steegers-TheunissenRPM, BoersGHJ, TrijbelsFJM, EskesTKAB. Neural-tube defects and derangement of homocysteine metabolism. New Engl J Med324:199–200, 1991.
185.
Van der PutNMJ, Steegers-TheunissenRPM, FrosstP, TrijbelsFJM, EskesTKAB, Van den HeuvelLP, MarimanECM, Den HeyerM, RozenR, BlomHJ. Mutated methylenetetrahydrofolate reductase as a risk factor for spina bifida. Lancet346:1070–1071, 1995.
186.
LucockMD, WildJ, LumbCH, OliverM, KendallR, DaskalakisI, SchorahCJ, LeveneMI. Risk of neural tube defect-affected pregnancy is associated with a block in maternal one-carbon metabolism at the level of N-5-methyltetrahydrofolate: homocysteine methyltransferase. Biochem Mol Med61:28–40, 1997.
187.
FinnellRH, GreerKA, BarberRC, PiedrahitaJA, ShawM, LammerEJ. Neural tube defects and craniofacial defects with special emphasis on folate pathway genes. Crit Rev Oral Biol Med9:38–53, 1998.
188.
HeilSG, Van der PutNMJ, TrijbelsFJM, GabreëlsFJM, BlomHJ. Molecular genetic analysis of human folate receptors in neural tube defects. Eur J Hum Genet7:393–396, 1999.
189.
BarberRC, ShawGM, LammerEJ, GreerKA, BielaTA, LaceySW, WassermanCR, FinnellRH. Lack of association between mutations in the folate receptor-alpha gene and spina bifida. Am J Med Genet76:310–317, 1998.
190.
GulatiS, ChenZ, BrodyLC, RosenblattDS, BanerjeeR.Defects in auxiliary redox proteins leads to functional methionine synthase deficiency. J Biol Chem272:19171–19175, 1997.
191.
ChenZ, BanerjeeR.Purification of soluble cytochrome b5 as a component of the reductive activation of porcine methionine synthase. J Biol Chem273:26248–26255, 1998.
192.
LeclercD, WilsonA, DumasR, GafuikC, SongD, WatkinsD, HengHHQ, RommensJM, SchererSW, RosenblattDS, GravelRA. Cloning and mapping of a cDNA for methionine synthase reductase, a flavoprotein defective in patients with homocystinuria. Proc Natl Acad Sci U S A95:3059–3064, 1998.
193.
SkovbyFN, KrassikoffN, FranckeU.Assignment of the gene for cystathionine β-synthase to human chromosome 21 in somatic cell hybrids. Hum Genet65:291–294, 1984.
194.
MunckeM, KrausJP, OhuraT, FranckeU.The gene for cystathionine β-synthase (CBS) maps to the subtelomeric region on chromosome 21q and to the proximal mouse chromosome 17. Am J Hum Genet42:550–559, 1988.
195.
KrausJP, LeK, SwaroopM, OhuraT, TaharaT, RosenbergE, RoperMD, KozichV.Human cystathionine β-synthase cDNA: Sequence, alternative splicing and expression in cultured cells. Hum Mol Genet2:1633–1638, 1993.
196.
KrausJP, OliveriusovaJ, SokolovaJ, KrausE, VlcekC, de FrancisR, MacleanKN, BaoL, Bukovsk, PattersonD, PacesV, AnsorgeW, KozichV.The human cystathionine β-synthase (CBS) gene: Complete sequence, alternative splicing and polymorphisms. Genomics52:312–324, 1998.
197.
QuerPV, RouillacC, JanbonC, LondonJ, DemailleJ, KamounP, DufferJL, AbitbolM, Chass. Spatial and temporal expression of the cystathionine beta-synthase gene during early human development. Biochem Biophys Res Commun254:127–137, 1999.
198.
SelhubJ, MillerJH. The pathogenesis of homocysteinemia: interruption of the coordinate regulation by S-adenosylmethionine of the remethylation and transsulfuration of homocysteine. Am J Clin Nutr55:131–138, 1992.
199.
RamsbottomD, ScottJM, WeirDG, KirkePN, MillsJI, GallagherPM, WhiteheadAS. Are common mutations of cystathionine β-synthase involved in the aetiology of neural tube defects?Clin Genet51:39–42, 1997.
200.
ScottJM, McPartlinJ, MolloyA, McNultyH, HalliganA, DarlingM, WeirDG. Folate metabolism in pregnancy. Adv Exp Med Biol338:727–732, 1993.
201.
LiYN, GulatiS, BakerPJ, BrodyLC, BanerjeeR, KrugerWD. Cloning, mapping and RNA analysis of the human methionine synthase gene. Hum Mol Genet5:1851–1858, 1996.
202.
LeclercD, CampeauE, GoyetteP, AdjallaCE, ChristensenB, RossM, EydouxP, RosenblattDS, RozenR, GravelRA. Human methionine synthase: cDNA cloning and identification of mutations in patients of the cbIG complementation group of folate/cobalamin disorders. Hum Mol Genet5:1867–1874, 1996.
203.
GulatiS, BakerP, LiYN, FowlerB, KrugerWD, BrodyLC, BanerjeeR.Defects in human methionine synthase in cblG patients. Hum Mol Genet5:1859–1865, 1996.
204.
WilsonA, LeclercD, SaberiF, CampeauE, HwangHY, ShaneB, PhillipsJAIII, RosenblattDS, GravelRA. Functionally null mutations in patients with the cbIG-variant form of methionine synthase deficiency. Am J Hum Genet63:409–414, 1998.
205.
BorcsokE, AbelesRH. Mechanism of action of cystathionine β-synthase. Arch Biochem Biophys213:695–707, 1982.
206.
ScottJM. Folate-vitamin B12 interrelationships in the central nervous system. Proc Nutr Soc51:219–224, 1992.
207.
ShinYS, BuehringKU, StokstadELR. The relationship between vitamin B12 and folic acid and the effect of methionine on folate metabolism. Mol Cell Biochem9:97–108, 1975.
208.
SchorahCJ, SmithellsRW, ScottJ.Vitamin B12 and anencephaly. Lanceti:880, 1980.
209.
Gardiki-KouidouP, SellerMJ. Amniotic fluid folate, vitamin B12 and transcobalamins in neural tube defects. Clin Genet33:441–448, 1998.
210.
MagnusP, MagnusEM, BergK.Transcobalamins in the etiology of neural tube defects. Clin Genet39:309–310, 1991.
211.
EconomidesDL, FergusonJ, MackenzieIZ, DarleyJ, WareII, Holmes-SiedleM.Folate and vitamin B12 concentrations in maternal and fetal blood, and amniotic fluid in second trimester pregnancies complicated by neural tube defects. Br J Obstet Gynaecol99:23–25, 1992.
212.
AdamsMJJr., KhouryMJ, ScanlonKS, StevensonRE, KnightGJ, HaddowJE, SylvesterGC, CheekJE, HenryJP, StablerSP. Elevated midtrimester serum methylmalonic acid levels as a risk factor for neural tube defects. Teratology51:311–317, 1995.
213.
DawsonEB, EvansDR, Van HookJW. Amniotic fluid B12 and folate levels associated with neural tube defects. Am J Perinatol15:511–514, 1998.
214.
SteenMT, BoddieAM, FischerAJ, MacmahonW, SaxeD, SullivanKM, DemburePP, ElsasLJ. Neural-tube defects are associated with low concentrations of cobalamin (vitamin B12) in amniotic fluid. Prenat Diagn18:545–555, 1998.
215.
Van der PutNMJ, van der MolenEF, KluijtmansLAJ, HeilSG, TrijbelsFJM, EskesTKAB, van Oppenraaij-EmmerzaalD, BanerjeeR, BlomHJ. Sequence analysis of the coding region of human methionine synthase: Relevance to hyperhomocysteinaemia in neural-tube defects and vascular diseaseQ J Med90:511–517, 1997.
216.
MorrisonK, EdwardsYH, LynchSA, BurnJ, HolF, MarimanE.Methionine synthase and neural tube defects. J Med Genet34:958, 1997.
217.
ChristensenB, ArbourL, TranP, LeclercD, SabbaghianN, PlattR, GilfixBM, RosenblattDS, GravelRA, ForbesP, RozenR.Genetic polymorhisms in methylenetetrahydrofolate reductase and methionine synthase, folate levels in red blood cells, and risk of neural tube defects. Am J Med Genet84:151–157, 1999.
218.
BrodyLC, BakerPJ, ChinesPS, MusickA, MolloyAM, SwansonDA, KirkePN, GhoshS, ScottJM, MillsJL. Methionine synthase: High-resolution mapping of the human gene and evaluation as a candidate locus for neural tube defects. Mol Genet Metab67:324–333, 1999.
219.
HarmonDL, ShieldsDC, WoodsideJV, McMasterD, YarnellJW, YoungIS, PengK, ShaneB, EvansAE, WhiteheadAS. Methionine synthase D919G polymorphism is a significant but modest determinant of circulating homocysteine concentrations. Genet Epidemiol17:298–309, 1999.
220.
WilsonA, PlattR, WuQ, LeclercD, ChristensenB, YangH, GravelRA, RozenR.A common variant in methionine synthase reductase combined with low cobalamin (vitamin B12) increases risk for spina bifida. Mol Genet Metab67:317–323, 1999.
221.
KutzbachC, StokstadELR. Feedback inhibition of methylenetetrahydrofolate reductase in rat liver by S-adenosylmethionine. Biochim Biophys Acta139:217–220, 1967.
222.
MatthewsRG, BaughCM. Interactions of pig liver methylenetetrahydrofolate reductase with methylenetetrahydropteroyl polyglutamate substrates and with dihydropteroylpolyglutamate inhibitors. Biochemistry19:2040–2045, 1980.
223.
MatthewsRG. Are the redox properties of tetrahydrofolate cofactors utilized in folate-dependent reactions?Fed Proc41:2600–2604, 1982.
224.
LewisGP, RowePB. Methylenetetrahydrofolate reductase: Studies in a human mutant and mammalian liver. In: Blair JA, Ed. Chemistry and Biology of Pteridines. Berlin, de Gruyter, p229, 1983.
225.
GoyetteP, SumnerJS, MilosR, DuncanAMV, RosenblattDS, MatthewsRG, RozenR.Human methylenetetrahydrofolate reductase: Isolation of cDNA, mapping and mutation identification. Nat Genet7:195–200, 1994.
226.
GoyetteP, PaiA, MilosR, FrosstP, TranP, ChenZ, ChanM, RozenR.Gene structure of human and mouse methylenetetrahydrofolate reductase (MTHFR). Mamm Genome9:652–656, 1998.
227.
SmithI, HylandK, KendallB.Clinical role of pteridine therapy in tetrahydrobiopterin deficiency. J Inherited Metab Dis8(suppl I):39–45, 1985.
228.
KangS-S, WongPWK, SusmanoA, SoraJ, NurusisM, RuggieN.Thermolabile methylenetetrahydrofolate reductase: An inherited risk-factor for coronary artery disease. Am J Hum Genet48:536–545, 1991.
229.
FrosstP, BlomHJ, MilosR, GoyetteP, SheppardCA, MatthewsRG, BoersGJH, den HeijerM, KluijtmansLAJ, van den HeuvelLP, RozenR.A candidate genetic risk-factor for vascular disease: A common mutation in methylenetetrahydrofolate reductase. Nat Genet10:111–113, 1995.
230.
KangS-S, ZhouJ, WongPWK, KowalisynJ, StrokoschG.Intermediate homocysteinemia: a thermolabile variant of methylenetetrahydrofolate reductase. Am J Hum Genet43:414–421, 1988.
231.
NelenWLDM, BlomHJ, ThomasCMG, SteegersEAP, BoersGHJ, EskesTKAB. Methylenetetrahydrofolate reductase polymorphism affects the change in homocysteine and folate concentrations resulting from low dose folic acid supplementation in women with unexplained recurrent miscarriages. J Nutr128:1336–1341, 1998.
232.
Van der PutNMJ, Van den HeuvelLP, Steegers-TheunissenRPM, TrijbelsFJM, EskesTKAB, MarimanECM, Den HeyerM, BlomHJ. Decreased methylenetetrahydrofolate reductase activity due to the C677T mutation in families with spina bifida offspring. J Mol Med74:691–694, 1996.
233.
Van der PutNMJ, TrijbelsFJM, HolF, EskesTKAB, Steegers-TheunissenRPM, van den HeuvelLPWJ, MarimanECM, BlomHJ. Mutated methylenetetrahydrofolate reductase in sporadic and hereditary spina bifida offspring. In MatoJM, CaballeroA, Ed. Proceedings of Workshop on Methionine Metabolism, Molecular Mechanism and Clinical Implications. Consejo Superior de Investigaciones Cientificas, Madrid, p186–191, 1996.
234.
Van der PutNMJ, EskesTKAB, BlomHJ. Is the common C677T mutation in the methylenetetrahydrofolate reductase gene a risk factor for neural tube defects?A meta-analysis Q J Med90:111–115, 1997.
235.
WhiteheadAS, GallagherP, MillsJL, KirkePN, BurkeH, MolloyAM, WeirDG, ShieldsDC, ScottJM. A genetic defect in 5,10-methylenetetrahydrofolate reductase in neural tube defects. Q J Med88:763–766, 1995.
236.
OuCY, StevensonRF, BrownVK, SchwartzCE, AllenWP, KhouryM, OakleyGP, AdamsMJ. C677T homozygosity associated with thermolabile 5,10-methylenetetrahydrofolate reductase as a risk factor for neural tube defects. Am J Hum Genet57(suppl):A223, 1995.
237.
De FranchisR, SebastioG, MandatoC, AndriaG, MastroiacovoP.Spina bifida, C677T mutation, and role of folate. Lancet346:1703, 1995.
238.
De FranchisR, BuonincontiA, MandatoC, PepeA, SperandeoMP, Del GadoR, CapraV, SalvaggioE, AndriaG, MastroiacovoP.The C677T mutation of the 5,10-methylenetetrahydrofolate reductase gene is a moderate risk factor for spina bifida in Italy. J Med Genet35:1009–1013, 1998.
WilckenDEL, WangXL. Relevance to spina bifida of mutated methylenetetrahydrofolate reductase. Lancet347:340, 1996.
241.
MornetE, MullerF, Lenvoise-FuretA, DelezoideAL, ColJY, Simon-BouyB, SerreJL. Screening of the C677T mutation on the methylenetetrahydrofolate reductase gene in French patients with neural tube defects. Hum Genet100:512–514, 1997.
242.
ShawGM, RozenR, FinnellRH, WassermanCR, LammerEJ. Maternal vitamin use, genetic variation of infant methylenetetrahydrofolate reductase, and risk for spina bifida. Am J Epidemiol148:30–37, 1998.
243.
UbbinkJB, ChristiansonA, BesterMJ, Van AllenMI, VenterPA. DelportR, BlomH, MerweA, PotgieterH, VermaakWJ. Folate status, homocysteine metabolism, and methylenetetrahydrofolate reductase in rural South African blacks with a history of pregnancy complicated by neural tube defects. Metabolism48:269–274, 1999.
244.
WilckenDEL. MTHFR C677T mutation, folate intake, neural-tube defect, and risk of cardiovascular disease. Lancet350:603–604, 1997.
245.
JohnsonWG, StenroosES, HeathSC, ChenY, CarrollR, McKoyV, ChatkuptS, LehnerT.Distribution of alleles of the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism in familial spina bifida. Am J Med Genet87:407–412, 1999.
246.
ChristensenB, ArbourL, TranP, LeclercD, SabbaghianN, PlattR, GilfixBM, RosenblattDS, GravelRA, ForbesP, RozenR.Genetic polymorphism in methylenetetrahydrofolate reductase and methionine synthase, folate levels in red blood cells, and risk of neural tube defects. Am J Med Genet84:151–157, 1999.
247.
KochMC, StegmannK, ZieglerA, SchroterB, ErmertA.Evaluation of the MTHFR C677T allele and the MTHFR gene locus in a German spina bifida population. Eur J Pediatr157:487–492, 1998.
248.
ShieldsDC, KirkePN, MillsJL, RamsbottomD, MolloyAM, BurkeH, WeirDG, ScottJM, WhiteheadAS. The thermolabile variant of methylenetetrahydrofolate reductase and neural tube defects: An evaluation of genetic risk and the relative importance of the genotype of the embryo and the mother. Am J Hum Genet64:1045–1055, 1999.
249.
Van der PutNMJ, GabreëlsF, StevensEMB, SmeitinkJAM, TrijbelsFJM, EskesTKAB, van den HeuvelLP, BlomHJ. A second common mutation in the methylenetetrahydrofolate reductase gene: A risk factor for neural tube defects?Am J Hum Genet62:1044–1051, 1998.
250.
WeisbergI, TranP, ChristensenB, SibaniS, RozenR.A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab64:169–172, 1998.
251.
StegmannK, ZieglerA, NgoETKM, KohlschmidtN, SchroterB, ErmertA, KochMC. Linkage disequilibrium of MTHFR genotypes 677C/T-1298A/C in the German population and association studies in probands with neural tube defects (NTD). Am J Med Genet87:23–29, 1999.
252.
BottoLD, MastroiacovoP.Exploring gene-gene interactions in the etiology of neural tube defects. Clin Genet53:456–459, 1998.
253.
SpeerMC, NyeJ, McLoneD, WorleyG, MelvinEC, VilesKD, FranklinA, DrakeC, MacKeyJ, GeorgeTM. Possible interaction of genotypes at cystathionine beta-synthase (CBS) and methylenetetrahydrofolate reductase (MTHFR) in neural tube defects: NTD Collaborative Group. Clin Genet56:142–144, 1999.
254.
SelhubJ, JacquesPF, WilsonPWF, RushD, RosenbergIH. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. J Am Med Assoc270:2693–2698, 1993.
255.
HerbertV, ColmanN, JacobE.Folic acid and vitamin B12. In: GoodhartRS, ShilsME, Eds. Modern Nutrition in Health and Disease. Philadelphia: Lea and Febiger, pp229–259, 1980.
256.
Van AertsLAGJM, KlaasboerHH, PostmaNS, PertijsJCLM, PeereboomJHJC, EskesTKAB, NoordhoekJ.Stereospecific in vitro embryotoxicity of L-homocysteine in pre- and post-implantation rodent embryos. Toxicol in Vitro7:743–749, 1993.
257.
Van AertsLAGJM, BlomHJ, DeabreuRA, TrijbelsFJM, EskesTKAB, Peereboom-StegemanJHJC, NoordhoekJ.Prevention of neural tube defects by and toxicity of L-homocysteine in cultured postimplantation rat embryos. Teratology50:348–360, 1994.
258.
RosenquistTH, RatashakSA, SelhubJ.Homocysteine induces congenital defects of the heart and neural tube: Effect of folic acidProc Natl Acad SciU S A93:15227–15232, 1996.
259.
MonkM, BoubelikM, LehnertS.Temporal and regional changes in DNA methylation in the embryonic, extraembryonic and germ cell lineages during mouse embryo development. Development99:371–382, 1987.
260.
ShawGM, VelieEM, SchafferD.Is dietary intake of methionine associated with a reduction in risk for neural tube defect-affected pregnancies?Teratology56:295–299, 1997.
261.
CoelhoCND, KleinNW. Methionine and neural tube closure in cultured rat embryos: Morphological and biochemical analyses. Teratology42:437–451, 1990.
262.
Morriss KayG, TuckettF.The role of microfilaments in cranial neurulation in rat embryos: effects of short-term exposure to cytochalasin D. J Embryol Exp Morphol88:333–348, 1985.
263.
MatsudaM, KeinoH.An open cephalic neural tube reproducibly induced by cytochalasin D in rat embryos in vitro.Zool Sci11:547–553, 1994.
264.
GreeneND, CoppAJ. Inositol prevents folate-resistant neural tube defects in the mouse. Nat Med3:60–66, 1997.
265.
EssienFB, WannbergSL. Methionine but not folinic acid or vitamin-B12 alters the frequency of neural tube defects in Axd mutant mice. J Nutr123:27–34, 1993.
266.
PeetersMCE. Embryonic axial curvature: Relationships to neuropore closure. In: PeetersMCE, Ed. Embryonic axial curvature: relationship to neuropore closure. Datawyse Maastricht, Universitaire Pers Maastricht, The Netherlands, pp9–25, 1998.
267.
RosenblattDS. Inherited disorders of folate transport and metabolism. In: ScriverCR, BeaudetAL, SlyWS, ValleD, Eds. The Metabolic and Molecular Bases of Inherited Disease, 7th edition. New York: McGraw-Hill, pp2049–2064, 1989.
268.
Van AertsLAGJM. Investigation, using rat embryo culture, of the role of methionine supply in folic acid-mediated prevention of neural tube defects. Toxicol in Vitro9:677–684, 1995.
