Analysis of select folate pathway genes,PAX3, and humanT in a midwestern neural tube defect population

Trembath, Dimitri G.; Sherbondy, Andrea L.; Vandyke, Don C.; Shaw, Gary M.; Todoroff, Karen; Lammer, Edward J.; Finnell, Richard H.; Marker, Stephen; Lerner, Gary; Murray, Jeffrey C.

doi:10.1002/(sici)1096-9926(199905)59:5<331::aid-tera4>3.0.co;2-l

Cited by 87 publications

(1 citation statement)

References 30 publications

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“…Association studies of other candidate genes, such as folate receptor alpha and beta, have not been reported for human pregnancies exposed to AEDs. While differential expression of their equivalents in preclinical models has been postulated to account for some of the varying susceptibility to valproate teratogenicity (Finnell et al 1997), no evidence for an association with neural tube defects has been noted in non‐AED‐exposed populations (Trembath et al 1999). Furthermore, periconceptional supplementation with folic acid for human pregnancies exposed to AEDs does not seem to reduce the risk of other birth defects associated with folate deficiency (Hernandez‐Diaz et al 2000).…”

Section: What Can We Tell Patients Using Genetic Information?mentioning

confidence: 99%

Genetics of epilepsy: Epilepsy Research Foundation workshop report

Sisodiya

Cross

Blümcke

et al. 2007

Epileptic Disorders

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The Sixth Epilepsy Research Foundation workshop, held in Oxford in March 2006, brought together basic scientists, geneticists, epidemiologists, statisticians, pharmacologists and clinicians to consider progress, issues and strategies for harnessing genetics to improve the understanding and treatment of the epilepsies. General principles were considered, including the fundamental importance of clear study design, adequate patient numbers, defined phenotypes, robust statistical data handling, and follow‐up of genetic discoveries. Topics where some progress had been made were considered including chromosomal abnormalities, neurodevelopment, hippocampal sclerosis, juvenile myoclonic epilepsy, focal cortical dysplasia and pharmacogenetics. The ethical aspects of epilepsy genetics were reviewed. Principles and limitations of collaboration were discussed. Presentations and their matched discussions are produced here. There was optimism that further genetic research in epilepsy was not only feasible, but might lead to improvements in the lives of people with epilepsy.

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Section: What Can We Tell Patients Using Genetic Information?mentioning

confidence: 99%

Genetics of epilepsy: Epilepsy Research Foundation workshop report

Sisodiya

Cross

Blümcke

et al. 2007

Epileptic Disorders

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Apparent lability of neural tube closure in laboratory animals and humans

1999

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Neural tube defects (NTDs), a set of structural abnormalities affecting the brain, spinal cord, and the skeletal and connective tissues that protect them, are common malformations among humans and laboratory animals. The embryogenesis of the neural tube is presented to convey the complexity of the phenomenon, the multiplicity of requisite cellular and subcellular processes, and the precise timing of events that must occur for successful neural tube development. Interruption, even transitory, of any of these intricate processes or disruption of an embryo's developmental schedule can lead to an NTD. The population distribution of human NTDs demonstrates that genetic predisposition functions in susceptibility to NTDs. Data from animal studies support these concepts. NTDs are common outcomes in developmental toxicity safety assessments, occurring among control and treated groups. Numerous agents have caused increased levels of NTDs in laboratory animals, and species with shorter gestational periods appear more prone to toxicant-induced NTDs than those with longer gestations. Data from post-implantation whole embryo culture, although not predictive of human risk, are useful in studying neurulation mechanisms and in demonstrating the importance of maintaining embryonic schedules of development. We conclude that the concept that NTDs are produced by only a few toxicants that selectively target the developing nervous system is untenable. Rather, the combination of the time in gestation that an agent is applied, its dose, and its ability to disrupt critical processes in neurulation leads to NTDs. We further conclude that, because of both the relatively high prevalence and the multifactorial nature of NTDs, the mere occurrence of an NTD is insufficient for inferring that the defect was caused by an exogenous agent.

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Association between historically high frequencies of neural tube defects and the humanT homologue of mouseT (Brachyury)

et al. 2000

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The human T developmental gene has been implicated in the etiology of neural tube defects (NTDs) on the basis both of mouse studies of its homologue, T (Brachyury), and of allelic association in a Caucasian population. We have investigated the frequency of the T allelic variant TIVS7-2 in 218 Irish NTD case-parent triads. This population showed the same trend as previously reported, with an excess of the TIVS7-2 allele among cases. Log-linear modeling of case and maternal genotypic effects within families indicated that TIVS7-2 was elevated in cases (relative risk, RR = 1.36) but not in mothers (RR = 0.91). The TIVS7-2 allele is markedly associated with cases born before 1980 (RR = 2.09; CI = 1.23-3.55; corrected p = 0.030), but not with more recent cases (RR = 0.92). Cases carrying a TIVS7-2 allele did not show any increased tendency to be homozygous for the thermolabile variant of the folate-dependent enzyme 5,10-methylene tetrahydrofolate reductase, which is an established genetic risk factor for NTDs. Since the incidence of NTDs has declined markedly in Ireland over the last few decades, we suggest that the T-associated risk is potentiated by nutritional or environmental risk factor(s), the impact of which have been diminishing over time.

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Analysis of select folate pathway genes,PAX3, and humanT in a midwestern neural tube defect population

Cited by 87 publications

References 30 publications

Genetics of epilepsy: Epilepsy Research Foundation workshop report

Genetics of epilepsy: Epilepsy Research Foundation workshop report

Apparent lability of neural tube closure in laboratory animals and humans

Association between historically high frequencies of neural tube defects and the humanT homologue of mouseT (Brachyury)

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