Modifier locus for exencephaly in Cecr2 mutant mice is syntenic to the 10q25.3 region associated with neural tube defects in humans

2007 ◽  
Vol 31 (2) ◽  
pp. 244-251 ◽  
Author(s):  
Courtney E. Davidson ◽  
Qian Li ◽  
Gary A. Churchill ◽  
Lucy R. Osborne ◽  
Heather E. McDermid
Keyword(s):  
Spina Bifida ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Genetic Background ◽  
Single Gene ◽  
Neural Tube Closure ◽  
Whole Genome ◽  
Chromosome 19 ◽  
Modifier Locus ◽  
Splotch Mutation

Neural tube defects (NTDs), the second most common birth defect in humans, are multifactorial with complex genetic and environmental causes, although the genetic factors are almost completely unknown. In mice, >100 single gene mutations cause NTDs; however, the penetrance in many of these single gene mutant lines is highly dependent on the genetic background. We previously reported that a homozygous Cecr2 mutation on a BALB/c background causes exencephaly at a frequency of 74% compared with 0% on an FVB/N background. We now report that a major genetic modifier on chromosome 19, mapped using whole genome linkage analysis, increases the relative risk of exencephaly by 3.74 times in homozygous BALB embryos vs. BALB/FVB heterozygotes. Scanning electron microscopy revealed that the modifier does not affect the location of neural tube closure site 2, a known murine susceptibility factor for exencephaly. Crossing the Sp ( Splotch) mutation in the Pax3 gene onto the FVB/N background for two generations indicated that this resistant strain also decreases the penetrance of spina bifida. The chromosome 19 modifier region corresponds to a linkage region on human chromosome 10q25.3 mapped in a whole genome scan of human NTD families. Since the FVB/N genetic background affects susceptibility to both exencephaly and spina bifida, the human homolog of the chromosome 19 modifier locus may be a better candidate for human NTD susceptibility factors than genes that when mutated actually cause NTDs in mice.

scholarly journals MiR-324–5p Regulation in Disturbed Embryogenesis Induced by Folate Deficiency

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1279-1279
Author(s):  
Li Wang ◽  
Shao-Yan Chang ◽  
Ting Zhang
Keyword(s):  
Dna Methylation ◽  
Spina Bifida ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Target Genes ◽  
Folate Deficiency ◽  
Neural Tube Closure ◽  
Shanxi Province ◽  
Mice Model ◽  
Deficiency Group

Abstract Objectives Folate plays key role during embryogenesis. It is proved that folate deficiency is a risk factor for birth defects mainly exerting its effects through DNA methylation. Here, we want to discover the epigenetic process of DNA methylation in the regulation of miRNAs and thereby regulates neural tube closure through actions on target genes. Methods 40 fetuses with spina bifida and 46 control fetuses from Shanxi Province in China were enrolled to study miR-324–5p alternations with folate deficiency. Meanwhile, mice model with folate deficiency diet were built to study the effects and possible mechanisms of pregnancy folate deficiency. Overexpressed miR-324–5p zebras model were used to detected the role of miR-324–5p during embryogenesis. And disturbed folic acid metabolism cell and mice model were used to confirm the mechanisms of miR-324–5p in neural tube defects induced by folate deficiency. Results We observed decreased miR-324–5p methylation in the brains of individuals with spina bifida. Hypomethylation of miR-324–5 increased the risk of spina bifida, with an odds ratio of 7.0 (95% CI: 2.10–23.36; P < 0.0001). A positive correlation between miR-324–5p methylation and folate levels were verified, and higher folate concentration reversed miR-324–5p alternations. We also observed increased miR-324–5p expression in the folate deficiency group, with concomitant decreased expression of its putative target genes, GLI1 and SMO. Furthermore, overexpression of miR-324–5p induced neural tube defects with inhibition of cell proliferation and migration. Similarly, we confirmed suppression of GLI1 and SMO expression in the brain of individuals with spina bifida. Conclusions The effect of folate deficiency on neural tube development may be mediated by miR-324–5p and its target genes. Funding Sources The National Natural Science Fund of China (81,670,802/H0724), National Key Research and Developmwnt Program (2016YFC1000502).

Neural Tube Defects

2018 ◽  
Author(s):  
Jimmy Hoang ◽  
Samuel David Yanofsky
Keyword(s):  
Spina Bifida ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Congenital Abnormalities ◽  
Spinal Dysraphism ◽  
Neural Tube Closure ◽  
Increased Risk ◽  
Spina Bifida Cystica ◽  
The Brain ◽  
Is Failure

Neural tube defects (NTDs) are congenital abnormalities that arise from the neural tube failing to close. These defects can affect the brain, spine, or spinal cord and generally happen within the first month of pregnancy. Cranial dysraphism is failure of cranial neural tube closure and includes anencephaly and encephalocele. Spinal dysraphism is failure of caudal neuropore closure and includes spina bifida cystica and occulta. Myelomeningocele is a type of spina bifida cystica where the membranous sac containing neural tissue protrudes through an opening in the back. It is the most common NTD and considered a surgical emergency due to the increased risk for infection, further neurologic damage, and dehydration. Advancements in medicine have allowed for the possibility of early diagnosis and even in utero surgical intervention. This chapter focuses more exclusively on the approach and management of myelomeningocele.

Interaction between splotch (Sp) and curly tail (ct) mouse mutants in the embryonic development of neural tube defects

Development ◽  
1993 ◽  
Vol 119 (1) ◽  
pp. 113-121 ◽  
Author(s):  
J.P. Estibeiro ◽  
F.A. Brook ◽  
A.J. Copp
Keyword(s):  
Spina Bifida ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Chain Reaction ◽  
Mouse Mutants ◽  
Posterior Neuropore ◽  
Curly Tail ◽  
Polymerase Chain ◽  
Splotch Mutation ◽  
Severe Disturbance

The mouse mutations splotch (Sp) and curly tail (ct) both produce spinal neural tube defects with closely similar morphology, but achieve this by different embryonic mechanisms. To determine whether the mutants may interact during development, we constructed mice carrying both mutations. Double heterozygotes exhibited tail defects in 10% of cases, although the single heterozygotes do not express this phenotype. Backcrosses of double heterozygotes to ct/ct produced offspring with an elevated incidence of neural tube defects, both spina bifida and tail defects, compared with a control backcross in which Sp was not involved. Use of the deletion allele Sp2H permitted embryos carrying a splotch mutation to be recognised by polymerase chain reaction assay. This experiment showed that only embryos carrying Sp2H develop spina bifida in the backcross with ct/ct, suggesting that the genotype Sp2H/+, ct/ct is usually lethal around the time of birth as a result of severe disturbance of neurulation. The interaction between Sp and ct was investigated further by examining embryos in the backcross for developmental markers of the Sp/Sp and ct/ct genotypes. Sp/Sp embryos characteristically lack neural crest derivatives, such as dorsal root ganglia, and die on day 13 of gestation. Double mutant embryos from the backcross did not exhibit either of these characteristics suggesting that homozygosity for ct does not cause Sp/+ embryos to develop as if they were of genotype Sp/Sp. The angle of ventral curvature of the posterior neuropore region is enhanced in affected ct/ct embryos whereas it was found to be reduced in Sp/Sp embryos compared with their normal littermates.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Novel mouse model of encephalocele: post-neurulation origin and relationship to open neural tube defects

2019 ◽  
Author(s):  
Ana Rolo ◽  
Gabriel L. Galea ◽  
Dawn Savery ◽  
Nicholas D. E. Greene ◽  
Andrew J. Copp
Keyword(s):  
Spina Bifida ◽  
Mouse Model ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Small Gtpase ◽  
Late Gestation ◽  
Neural Tube Closure ◽  
Surface Ectoderm ◽  
Open Spina Bifida ◽  
Tube Closure

ABSTRACTEncephalocele is a clinically important birth defect that can lead to severe disability in childhood and beyond. The embryonic pathogenesis of encephalocele is poorly understood and, while usually classified as a ‘neural tube defect’, there is conflicting evidence on whether encephalocele results from defective neural tube closure, or is a post-neurulation defect. It is also unclear whether encephalocele can result from the same causative factors as anencephaly and open spina bifida, or whether it is aetiologically distinct. This lack of information results largely from the scarce availability of animal models of encephalocele, particularly ones that resemble the commonest, non-syndromic human defects. Here we report a novel mouse model of occipito-parietal encephalocele, in which the small GTPase Rac1 is conditionally ablated in the (non-neural) surface ectoderm. Most mutant fetuses have open spina bifida, and some also exhibit exencephaly/anencephaly. However, a large proportion of mutant fetuses exhibit encephalocele affecting the occipito-parietal region. The encephalocele phenotype does not result from a defect in neural tube closure, but rather from a later disruption of the surface ectoderm covering the already closed neural tube, allowing the brain to herniate. The neuroepithelium itself shows no down-regulation of Rac1 and appears morphologically normal until late gestation. A large skull defect develops overlying the region of brain herniation. Our work provides a new genetic model of occipito-parietal encephalocele, particularly resembling non-syndromic human cases. While encephalocele has a different, later-arising pathogenesis than open neural tube defects, both can share the same genetic causation.SUMMARY STATEMENTEncephalocele - a severe brain defect - arises after neural tube closure, but can share a common genetic cause with anencephaly, a defect of neural tube closure.

Detection of spina bifida in the first trimester of gestation in association with triploidy

2017 ◽  
Author(s):  
K.K. Otaryan , C.G. Gagaev
Keyword(s):  
Spina Bifida ◽  
Early Detection ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
First Trimester ◽  
Termination Of Pregnancy ◽  
Diagnostic Tools ◽  
Prenatal Detection ◽  
Post Abortion

The case of prenatal detection of spina bifida at 12+3 weeks of gestation is described. Termination of pregnancy was performed at 13+3 weeks. Post-abortion karyotyping revealed triploidy (69XXX). Diagnostic tools for early detection of neural tube defects in the 1st trimester of gestation and subsequent appropriate management of pregnancy are discussed.

Neural Tube Defects: A Two-Pronged Approach to Primary Prevention

PEDIATRICS ◽  
1982 ◽  
Vol 70 (4) ◽  
pp. 648-650
Author(s):  
K. M. Laurence
Keyword(s):  
Folic Acid ◽  
Primary Prevention ◽  
Environmental Factors ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Genetic Background ◽  
Genetic Factors ◽  
Maternal Nutrition ◽  
Folic Acid Deficiency ◽  
Acid Deficiency

It is generally agreed that neural tube defects (NTD) have a multifactorial etiology when genetic factors render the developing fetus susceptible to intrauterine environmental factors acting during the fourth week of gestation to interfere with the orderly closure of the neural tube.1 As there is little likelihood that anything can be done about the genetic background, primary prevention would therefore be dependent on eliminating these factors from the environment or avoiding them. My intention here is to enlarge on some aspects of primary prevention of NTD as outlined by Smithells in an earlier issue (Pediatrics 69:498, 1982).2 One environmental factor, poor maternal nutrition and, more particularly, folic acid deficiency seems now to have been identified, but there are almost certainly a number of others.

scholarly journals Mengenal Spina Bifida dan Pencegahannya

2021 ◽  
Vol 1 (12) ◽  
pp. 896-903
Author(s):  
Genta Faesal Atsani ◽  
Zanetha Mauly Ilawanda ◽  
Ilma Fahira Basyir
Keyword(s):  
Spina Bifida ◽  
Birth Defects ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Congenital Abnormality ◽  
Congenital Abnormalities ◽  
Folic Acid Supplementation ◽  
Online Portal ◽  
The Brain ◽  
Developing Spinal Cord

Neural tube defects (NTD) are one of the birth defects or congenital abnormalities that occur in the brain and spine, and commonly find in newborns worldwide. Anencephaly and spina bifida are the two prevalent forms of NTD. The incidence of spina bifida happen on average 1 in 1000 cases of birth worldwide and there are 140,000 cases per year worldwide. Source searches were carried out on the online portal of journal publications as many as 20 sources from MedScape, Google Scholar and the Nation Center for Biotechnology Information / NCBI with the keywords “Neural tube defects (NTD), prevention, and spina bifida”. Spina bifida is a congenital abnormality that occurs in the womb due to a failure of closing process the neural tube during the first few weeks of embryonic development which causes the spine not completely close around the developing spinal cord nerves. NTD can ensue multifactorial conditions such as genetic, environmental, and folate deficiency. The use of folic acid supplementation starting at least 3 months before pregnancy, those are 400 mcg (0.4 mg) per day and 800 mcg per day during pregnancy can reduce the risk of developing neural tube defects such as spina bifida. Generally, spina bifida is undertaking by surgery and the regulation of patients comorbid. Public can find out prevention to avoid or reduce the risk of spina bifida so that the incidence of spina bifida can decrease along with the increasing awareness of the community regarding this disease.

Neural Tube Defects: Prevention by Vitamin Supplements

PEDIATRICS ◽  
1982 ◽  
Vol 69 (4) ◽  
pp. 498-499
Author(s):  
R. W. Smithells
Keyword(s):  
Neural Tube ◽  
Neural Tube Defects ◽  
Birth Defect ◽  
Epidemiologic Study ◽  
Neural Tube Closure ◽  
Additive Effects ◽  
Vitamin Supplements ◽  
Tube Closure

Neural tube defects (NTD) have been the object of more intense epidemiologic study than any other kind of birth defect. This is in part because of their ready recognition at birth (and, in recent years, before birth) and in part because their consequences are usually catastrophic: they kill or they cripple. Regarding their cause, no single genetic or environmental agent has been identified (or is likely to be) and a multifactorial basis is assumed. If failure of neural tube closure results from the additive effects of several adverse factors, removal or correction of any one might shift the developmental balance across the threshold from NTD to normality.

Prevalence of Neural Tube Defects (NTDs) In And Around Varanasi Region: Some Observations

2021 ◽  
Author(s):  
Vaibhav Pandey ◽  
Surendra Kumar Pandey ◽  
Praveen Kumar Tiwari ◽  
Pragati Shakya ◽  
Shashank Shekhar Jha ◽  
...  
Keyword(s):  
Neural Tube ◽  
Neural Tube Defects ◽  
Birth Defect ◽  
Neural Tube Closure ◽  
The World ◽  
Typical Type ◽  
Males And Females ◽  
One Year ◽  
Congenital Disabilities ◽  
Tube Closure

Abstract Congenital anomalies are one of the primary causes of infant mortality and disability in the world. Neural Tube Defects (NTDs) are the most typical type of birth defect resulting from the failure of Neural tube closure. In this retrospective hospital-based study, the data of the children affected byneural tube defects (NTDs) were analyzed. Prevalence of Hydrocephalous, Myelomeningocele (MMC), Encephalocele, Lipo MMC, Meningocele, Spina Bifida Occulta among children with more or less than one year of age and their occurrence in males and females was studied. The frequency of occurrence of cases of neural tube defects was significantly less among all the congenital disabilities, i.e., 5% of total cases studied. The prevalence of myelomeningocele, hydrocephalous, and Encephalocele was higher than other types of NTDs. This study concludes that the prevalence of hydrocephalous and myelomeningocele in this area raises a concern to have more research of their etiology.

Concanavalin A binding of alpha-fetoprotein in amniotic fluid as an aid in the diagnosis of neural tube defects.

1981 ◽  
Vol 27 (10) ◽  
pp. 1658-1660 ◽  
Author(s):  
P K Buamah ◽  
P Taylor ◽  
A M Ward
Keyword(s):  
Spina Bifida ◽  
Amniotic Fluid ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Concanavalin A ◽  
Gestational Age ◽  
Alpha Fetoprotein ◽  
Normal Outcome ◽  
Fetal Malformations ◽  
Open Spina Bifida

Abstract Concanavalin A nonreactive alpha-fetoprotein was determined in samples of amniotic fluid from 16 abnormal pregnancies complicated by anencephaly (7), open spina bifida (6), intra-uterine death (1), anencephaly with exomphalos (1), or open spina bifida with exomphalos (1), and in amniotic fluid from 50 normal pregnancies with gestational age between 13 and 24 weeks. In all 16 cases with fetal malformations, the proportion of nonreactive alpha-fetoprotein was significantly decreased (median 5.3%) as compared with amniotic fluid from pregnancies with a normal outcome (median 39.7%). The results confirm that this measurement is useful in the diagnosis of neural tube defects, especially when the concentration of alpha-fetoprotein in amniotic fluid is normal or only slightly above normal and gestational age is uncertain.

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