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PMID: 15939212 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Human neural tube defects: developmental biology, epidemiology, and genetics.

Neurotoxicology and teratology ·Vol. 27 ·No. 3 ·2005-00-00 ·Pages 515-24

Detrait ER, George TM, Etchevers HC, Gilbert JR, Vekemans M, Speer MC

Abstract

Birth defects (congenital anomalies) are the leading cause of death in babies under 1 year of age. Neural tube defects (NTD), with a birth incidence of approximately 1/1000 in American Caucasians, are the second most common type of birth defect after congenital heart defects. The most common presentations of NTD are spina bifida and anencephaly. The etiologies of NTDs are complex, with both genetic and environmental factors implicated. In this manuscript, we review the evidence for genetic etiology and for environmental influences, and we present current views on the developmental processes involved in human neural tube closure.

MeSH Terms
Animals Environment Female Humans Mice Nervous System/embryology Neural Tube Defects/epidemiology,genetics,pathology Pregnancy
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Detrait Eric R
Hôpital Necker, Enfants Malades Unité INSERM U393, 149, rue de Sèvres, 75743 Paris Cedex 15, France.
George Timothy M
Etchevers Heather C
Gilbert John R
Vekemans Michel
Speer Marcy C
References (87)
87 references, click to expand
  1. Promoter sequence, expression, and fine chromosomal mapping of the human gene (MLP) encoding the MARCKS-like protein: identification of neighboring and linked polymorphic loci for MLP and MACS and use in the evaluation of human neural tube defects.
    Genomics. 1998 Apr 15;49(2):253-64 PMID: 9598313
  2. Prenatally diagnosed neural tube defects: ultrasound, chromosome, and autopsy or postnatal findings in 212 cases.
    Am J Med Genet. 1998 May 26;77(4):317-21 PMID: 9600743
  3. Gene regulation of cell adhesion: a key step in neural morphogenesis.
    Brain Res Brain Res Rev. 1998 May;26(2-3):337-52 PMID: 9651550
  4. Low blood folates in NTD pregnancies are only partly explained by thermolabile 5,10-methylenetetrahydrofolate reductase: low folate status alone may be the critical factor.
    Am J Med Genet. 1998 Jun 30;78(2):155-9 PMID: 9674907
  5. Pax3 functions in cell survival and in pax7 regulation.
    Development. 1999 Apr;126(8):1665-74 PMID: 10079229
  6. Congenital malformations due to antiepileptic drugs.
    Epilepsy Res. 1999 Feb;33(2-3):145-58 PMID: 10094426
  7. Possible interaction of genotypes at cystathionine beta-synthase and methylenetetrahydrofolate reductase (MTHFR) in neural tube defects. NTD Collaborative Group.
    Clin Genet. 1999 Aug;56(2):142-4 PMID: 10517251
  8. Mini-review: toward understanding mechanisms of genetic neural tube defects in mice.
    Teratology. 1999 Nov;60(5):292-305 PMID: 10525207
  9. NEW SPLOTCH ALLELES IN THE MOUSE.
    J Hered. 1964 May-Jun;55:97-101 PMID: 14170406
  10. The thermolabile variant of methylenetetrahydrofolate reductase (MTHFR) is not a major risk factor for neural tube defect in American Caucasians. The NTD Collaborative Group.
    Neurogenetics. 1997 Sep;1(2):149-50 PMID: 10732818
  11. Neural tube defects and the 13q deletion syndrome: evidence for a critical region in 13q33-34.
    Am J Med Genet. 2000 Mar 20;91(3):227-30 PMID: 10756348
  12. Genetic studies in neural tube defects. NTD Collaborative Group.
    Pediatr Neurosurg. 2000 Jan;32(1):1-9 PMID: 10765131
  13. Mouse models for neural tube closure defects.
    Hum Mol Genet. 2000 Apr 12;9(6):993-1000 PMID: 10767323
  14. Clinical, genetic, and epidemiological factors in neural tube defects.
    Am J Hum Genet. 1988 Dec;43(6):827-37 PMID: 3195584
  15. Neurulation in the mouse: manner and timing of neural tube closure.
    Anat Rec. 1989 Feb;223(2):194-203 PMID: 2712345
  16. A mouse model for neural tube defects: the curtailed (Tc) mutation produces spina bifida occulta in Tc/+ animals and spina bifida with meningomyelocele in Tc/t.
    Teratology. 1989 Mar;39(3):303-12 PMID: 2658196
  17. Multivitamin/folic acid supplementation in early pregnancy reduces the prevalence of neural tube defects.
    JAMA. 1989 Nov 24;262(20):2847-52 PMID: 2478730
  18. Linkage strategies for genetically complex traits. II. The power of affected relative pairs.
    Am J Hum Genet. 1990 Feb;46(2):229-41 PMID: 2301393
  19. Linkage strategies for genetically complex traits. III. The effect of marker polymorphism on analysis of affected relative pairs.
    Am J Hum Genet. 1990 Feb;46(2):242-53 PMID: 2301394
  20. Neural tube defects: are neurulation and canalization forms causally distinct?
    Am J Med Genet. 1990 Mar;35(3):394-6 PMID: 2309788
  21. Cadmium teratogenicity and its relationship with metallothionein gene expression in midgestation mouse embryos.
    Toxicology. 1990 Oct;64(1):89-104 PMID: 2219135
  22. Molecular characterization of a deletion encompassing the splotch mutation on mouse chromosome 1.
    Genomics. 1991 May;10(1):89-93 PMID: 2045114
  23. Financial counseling for families of children with chronic disabilities.
    Dev Med Child Neurol. 1991 Aug;33(8):679-89 PMID: 1833252
  24. In-utero exposure to valproate and neural tube defects.
    Lancet. 1986 Jun 14;1(8494):1392-3 PMID: 2872511
  25. Neural tube defects, sex ratios, and X inactivation.
    Lancet. 1986 Dec 6;2(8519):1334-5 PMID: 2878199
  26. Can familial aggregation of disease be explained by familial aggregation of environmental risk factors?
    Am J Epidemiol. 1988 Mar;127(3):674-83 PMID: 3341366
  27. Are 'upper' and 'lower' neural tube defects aetiologically different?
    J Med Genet. 1988 Jul;25(7):503-4 PMID: 3050096
  28. Normal mouse strains differ in the site of initiation of closure of the cranial neural tube.
    Teratology. 1991 Aug;44(2):225-33 PMID: 1925982
  29. Splotch (Sp2H), a mutation affecting development of the mouse neural tube, shows a deletion within the paired homeodomain of Pax-3.
    Cell. 1991 Nov 15;67(4):767-74 PMID: 1682057
  30. Do familial neural tube defects breed true?
    J Med Genet. 1991 Sep;28(9):605-8 PMID: 1956058
  31. The biological chemistry of folate receptors.
    Blood. 1992 Jun 1;79(11):2807-20 PMID: 1586732
  32. Chromosomal mapping of the human (MACS) and mouse (Macs) genes encoding the MARCKS protein.
    Genomics. 1992 Sep;14(1):168-74 PMID: 1427822
  33. A mutation within intron 3 of the Pax-3 gene produces aberrantly spliced mRNA transcripts in the splotch (Sp) mouse mutant.
    Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):532-6 PMID: 8421686
  34. Is there etiologic heterogeneity between upper and lower neural tube defects?
    Am J Epidemiol. 1992 Dec 15;136(12):1493-501 PMID: 1288279
  35. Intermittent pattern of neural tube closure in two strains of mice.
    Teratology. 1993 Jan;47(1):73-80 PMID: 8475460
  36. Nucleotide sequence, expression, and chromosomal mapping of Mrp and mapping of five related sequences.
    Genomics. 1993 Jul;17(1):194-204 PMID: 8406449
  37. Upper and lower neural tube defects: an alternate hypothesis.
    J Med Genet. 1993 Oct;30(10):849-51 PMID: 8230161
  38. Evidence for multi-site closure of the neural tube in humans.
    Am J Med Genet. 1993 Oct 1;47(5):723-43 PMID: 8267004
  39. Study of genetics, epidemiology, and vitamin usage in familial spina bifida in the United States in the 1990s.
    Neurology. 1994 Jan;44(1):65-70 PMID: 8290094
  40. Valproic acid-induced neural tube defects.
    Ciba Found Symp. 1994;181:144-52; discussion 152-60 PMID: 8005022
  41. Folic acid metabolism and mechanisms of neural tube defects.
    Ciba Found Symp. 1994;181:180-7; discussion 187-91 PMID: 8005024
  42. Multifactorial inheritance of neural tube defects: localization of the major gene and recognition of modifiers in ct mutant mice.
    Nat Genet. 1994 Apr;6(4):357-62 PMID: 8054974
  43. Etiology and pathogenesis of human neural tube defects: insights from mouse models.
    Curr Opin Pediatr. 1994 Dec;6(6):624-31 PMID: 7849805
  44. Further evidence for an intermittent pattern of neural tube closure in humans.
    J Med Genet. 1995 Mar;32(3):205-7 PMID: 7783170
  45. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase.
    Nat Genet. 1995 May;10(1):111-3 PMID: 7647779
  46. Neural tube defects, chromosome abnormalities and multiple closure sites for the human neural tube.
    Clin Dysmorphol. 1995 Jul;4(3):202-7 PMID: 7551155
  47. Mutations in PAX3 that cause Waardenburg syndrome type I: ten new mutations and review of the literature.
    Am J Med Genet. 1995 Aug 28;58(2):115-22 PMID: 8533800
  48. A genetic defect in 5,10 methylenetetrahydrofolate reductase in neural tube defects.
    QJM. 1995 Nov;88(11):763-6 PMID: 8542260
  49. Aneuploidy among prenatally detected neural tube defects.
    Am J Med Genet. 1996 Jan 11;61(2):171-3 PMID: 8669447
  50. Methylenetetrahydrofolate reductase and neural tube defects.
    Lancet. 1996 Jul 6;348(9019):58 PMID: 8691945
  51. Hereditary factors in the etiology of neural tube defects. Results of a survey.
    Pediatr Neurosurg. 1995;23(6):311-6 PMID: 8744000
  52. A spinal cord fate map in the avian embryo: while regressing, Hensen's node lays down the notochord and floor plate thus joining the spinal cord lateral walls.
    Development. 1996 Sep;122(9):2599-610 PMID: 8787735
  53. Regional differences in morphogenesis of the neuroepithelium suggest multiple mechanisms of spinal neurulation in the mouse.
    Anat Embryol (Berl). 1996 Jul;194(1):65-73 PMID: 8800424
  54. Disruption of the mouse L1 gene leads to malformations of the nervous system.
    Nat Genet. 1997 Nov;17(3):346-9 PMID: 9354804
  55. Genetic landmarks for defects in mouse neural tube closure.
    Teratology. 1997 Sep;56(3):177-87 PMID: 9358605
  56. A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects?
    Am J Hum Genet. 1998 May;62(5):1044-51 PMID: 9545395
  57. 5,10-Methylenetetrahydrofolate reductase gene variants and congenital anomalies: a HuGE review.
    Am J Epidemiol. 2000 May 1;151(9):862-77 PMID: 10791559
  58. Neural tube closure in humans initiates at multiple sites: evidence from human embryos and implications for the pathogenesis of neural tube defects.
    Anat Embryol (Berl). 2000 Jun;201(6):455-66 PMID: 10909899
  59. Overexpression of murine Pax3 increases NCAM polysialylation in a human medulloblastoma cell line.
    J Biol Chem. 2000 Jul 28;275(30):23259-66 PMID: 10770948
  60. Domains of axin and disheveled required for interaction and function in wnt signaling.
    Biochem Biophys Res Commun. 2000 Oct 5;276(3):1162-9 PMID: 11027605
  61. Neural plate patterning: upstream and downstream of the isthmic organizer.
    Nat Rev Neurosci. 2001 Feb;2(2):99-108 PMID: 11253000
  62. The teratogenicity of anticonvulsant drugs.
    N Engl J Med. 2001 Apr 12;344(15):1132-8 PMID: 11297704
  63. Multifactorial genetics of exencephaly in SELH/Bc mice.
    Teratology. 2001 Oct;64(4):189-200 PMID: 11598925
  64. Circletail, a new mouse mutant with severe neural tube defects: chromosomal localization and interaction with the loop-tail mutation.
    Genomics. 2001 Nov;78(1-2):55-63 PMID: 11707073
  65. Neural tube defects in missed abortions: embryoscopic and cytogenetic findings.
    Am J Med Genet. 2002 Jan 1;107(1):52-7 PMID: 11807868
  66. Rescue of neural tube defects in Pax-3-deficient embryos by p53 loss of function: implications for Pax-3- dependent development and tumorigenesis.
    Genes Dev. 2002 Mar 15;16(6):676-80 PMID: 11914272
  67. The two sites of fusion of the neural folds and the two neuropores in the human embryo.
    Teratology. 2002 Apr;65(4):162-70 PMID: 11948562
  68. Identification of the mouse Loop-tail gene: a model for human craniorachischisis?
    Bioessays. 2002 Jul;24(7):580-3 PMID: 12111717
  69. Testing for genetic associations in a spina bifida population: analysis of the HOX gene family and human candidate gene regions implicated by mouse models of neural tube defects.
    Am J Med Genet. 2002 Jul 1;110(3):203-7 PMID: 12116226
  70. Parental occupation and neural tube defect-affected pregnancies among Mexican Americans.
    J Occup Environ Med. 2002 Jul;44(7):650-6 PMID: 12138876
  71. Risk of specific birth defects in relation to chlorination and the amount of natural organic matter in the water supply.
    Am J Epidemiol. 2002 Aug 15;156(4):374-82 PMID: 12181108
  72. Prevention of fumonisin B1-induced neural tube defects by folic acid.
    Teratology. 2002 Oct;66(4):169-76 PMID: 12353213
  73. Neural tube closure requires Dishevelled-dependent convergent extension of the midline.
    Development. 2002 Dec;129(24):5815-25 PMID: 12421719
  74. Gene expression profiling within the developing neural tube.
    Neurochem Res. 2002 Oct;27(10):1165-80 PMID: 12462415
  75. Embryonic expression of three mouse genes with homology to the Drosophila melanogaster prickle gene.
    Gene Expr Patterns. 2002 Nov;2(1-2):73-7 PMID: 12617840
  76. Updated investigations of the role of methylenetetrahydrofolate reductase in human neural tube defects.
    Clin Genet. 2003 Mar;63(3):210-4 PMID: 12694231
  77. The genetic basis of mammalian neurulation.
    Nat Rev Genet. 2003 Oct;4(10):784-93 PMID: 13679871
  78. Dorsal closure and convergent extension: two polarised morphogenetic movements controlled by similar mechanisms?
    Mech Dev. 2003 Nov;120(11):1385-93 PMID: 14623444
  79. Inositol- and folate-resistant neural tube defects in mice lacking the epithelial-specific factor Grhl-3.
    Nat Med. 2003 Dec;9(12):1513-9 PMID: 14608380
  80. Autoantibodies against folate receptors in women with a pregnancy complicated by a neural-tube defect.
    N Engl J Med. 2004 Jan 8;350(2):134-42 PMID: 14711912
  81. Changes in the mouse neuroepithelium associated with cadmium-induced neural tube defects.
    Teratology. 1980 Feb;21(1):79-88 PMID: 6247774
  82. Neural tube defects in France: segregation analysis.
    Am J Med Genet. 1982 Mar;11(3):287-98 PMID: 7081294
  83. Neural tube development in mutant (curly tail) and normal mouse embryos: the timing of posterior neuropore closure in vivo and in vitro.
    J Embryol Exp Morphol. 1982 Jun;69:151-67 PMID: 7119666
  84. Spinal dysraphia as an autosomal dominant defect in four families.
    Am J Med Genet. 1982 Aug;12(4):457-64 PMID: 6751087
  85. Possible causal heterogeneity in spina bifida cystica.
    Am J Med Genet. 1985 May;21(1):13-20 PMID: 4003438
  86. Vitamins: an evolutionary perspective.
    J Inherit Metab Dis. 1985;8 Suppl 1:2-7 PMID: 2931552
  87. Relationship between timing of posterior neuropore closure and development of spinal neural tube defects in mutant (curly tail) and normal mouse embryos in culture.
    J Embryol Exp Morphol. 1985 Aug;88:39-54 PMID: 4078540
Article Info
Journal
Neurotoxicology and teratology
Abbr.
Neurotoxicol Teratol
ISSN
0892-0362
DOI
10.1016/j.ntt.2004.12.007
Published
2005-00-00
Epub
2005-00-05
Pages
515-24
Language
English
Region
United States
NLM ID
8709538
PMCID
PMC2727639
Subset
IM
Grants
NINDS NIH HHS · R01 NS039818-05 · United States
NIEHS NIH HHS · U19 ES011375 · United States
NINDS NIH HHS · P01 NS026630 · United States
NICHD NIH HHS · P01 HD039948 · United States
NINDS NIH HHS · R01 NS039818 · United States
NICHD NIH HHS · P01 HD039948-010005 · United States
External Links
PubMed source DOI: 10.1016/j.ntt.2004.12.007 PMC Full Text View journal details
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