Service for Neurodevelopmental Disorders, Laboratory of Molecular Psychiatry and Neurogenetics, Department of Medicine, University Campus Bio-Medico, Rome, Italy.
Clin Genet. 2019 Feb;95(2):241-252. doi: 10.1111/cge.13421. Epub 2018 Sep 3.
There is growing evidence that epigenetic dysregulation plays a role in neurodevelopmental disorders. In humans, folate is one of the main donors of the methyl group required for the synthesis of S-adenosylmethionine, which in turn is needed for DNA and histone methylation as key neurodevelopment processes. Folate deficiency during pregnancy has been correlated with neural tube defects and with a higher incidence of neurocognitive and/or neurobehavioral deficits. A similar outcome may be exerted by gene polymorphisms in folate or folate-related pathways. This has been documented by numerous case/control association studies performed on neurodevelopmental disorders such as autism spectrum disorder and attention deficit hyperactivity disorder. In this regard, the folate cycle represents a "perfect model" of how genetics influences epigenetics. Gene variants in folate and folate-related pathways can be considered risk factors for neurodevelopmental disorders and should therefore be assessed by genetic testing in pregnant women. High-risk women should be considered for folate supplementation during pregnancy. Here, we review all published case/control association studies on gene polymorphisms in folate and folate-related pathways performed on neurodevelopmental disorders, provide an overview of neurodevelopment and DNA methylation changes occurring at this time, and describe the biological basis of neurodevelopmental disorders and recent evidence of their epigenetic dysregulation.
越来越多的证据表明，表观遗传失调在神经发育障碍中起作用。在人类中，叶酸是合成 S-腺苷甲硫氨酸所需的甲基供体之一，S-腺苷甲硫氨酸是 DNA 和组蛋白甲基化的关键神经发育过程所必需的。怀孕期间叶酸缺乏与神经管缺陷以及更高的神经认知和/或神经行为缺陷发生率相关。叶酸或叶酸相关途径中的基因多态性也可能产生类似的结果。大量针对神经发育障碍（如自闭症谱系障碍和注意缺陷多动障碍）的病例对照关联研究已经证明了这一点。在这方面，叶酸循环代表了遗传学如何影响表观遗传学的“完美模型”。叶酸和叶酸相关途径中的基因变异可以被认为是神经发育障碍的风险因素，因此应该在孕妇中进行基因检测。应考虑对高危孕妇在怀孕期间补充叶酸。在这里，我们回顾了所有已发表的关于叶酸和叶酸相关途径中的基因多态性在神经发育障碍中的病例对照关联研究，概述了此时发生的神经发育和 DNA 甲基化变化，并描述了神经发育障碍的生物学基础以及最近关于其表观遗传失调的证据。
