Pathobiology and genetics of neural tube defects
Pathobiology and genetics of neural tube defects
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DOI：
10.1046/j.1528-1157.44.s3.5.x
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发表时间：
2003-01-01
期刊：
影响因子：
5.6
通讯作者：
Spiegelstein, O
中科院分区：
文献类型：
--
作者：
Finnell, RH;Gould, A;Spiegelstein, O
目的：神经管缺陷（NTD），包括脊柱裂和无脑畸形，是常见的先天性畸形，发生在胚胎发育早期神经管未能实现适当的关闭。根据过去几十年获得的流行病学和临床数据，很明显，这些多因素缺陷的病因学具有重要的遗传成分，与特定的环境风险因素相互作用。这篇综述文章的目的是综合现有的文献上的遗传因素NTD risk.Results：迄今为止，有证据表明，关闭哺乳动物神经管启动和融合间歇性地在四个离散的位置。这四个位点中任何一个的这一过程的中断都可能导致NTD，可能是通过闭合位点特异性遗传机制产生的。参与神经管闭合的候选基因包括叶酸代谢途径的基因，以及参与叶酸transport.Conclusions：虽然广泛的努力集中在阐明NTDs的病因遗传风险因素，这些畸形的人口负担仍然未知。一个有NTD孩子的高风险群体是在怀孕期间接受抗癫痫药物治疗的癫痫妇女。努力更好地了解遗传因素，可能有助于他们的风险增加，以及神经管闭合缺陷的发病机制，在此进行审查。
Purpose: Neural tube defects (NTDs), including spina bifida and anencephaly, are common congenital malformations that occur when the neural tube fails to achieve proper closure during early embryogenesis. Based on epidemiological and clinical data obtained over the last few decades, it is apparent that these multifactorial defects have a significant genetic component to their etiology that interacts with specific environmental risk factors. The purpose of this review article is to synthesize the existing literature on the genetic factors contributing to NTD risk.Results: To date, there is evidence that closure of the mammalian neural tube initiates and fuses intermittently at four discrete locations. Disruption of this process at any of these four sites may lead to an NTD, possibly arising through closure site-specific genetic mechanisms. Candidate genes involved in neural tube closure include genes of the folate metabolic pathway, as well as those involved in folate transport.Conclusions: Although extensive efforts have focused on elucidating the genetic risk factors contributing to the etiology of NTDs, the population burden for these malformations remains unknown. One group at high risk for having children with NTDs is epileptic women receiving antiepileptic medications during pregnancy. Efforts to better understand the genetic factors that may contribute to their heightened risk, as well as the pathogenesis of neural tube closure defects, are reviewed herein.