Department of Translational Medicine and LTTA Centre, University of Ferrara, 44121 Ferrara, Italy.
University Center for Studies on Gender Medicine, University of Ferrara, 44121 Ferrara, Italy.
Genes (Basel). 2021 May 20;12(5):782. doi: 10.3390/genes12050782.
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition affecting behavior and communication, presenting with extremely different clinical phenotypes and features. ASD etiology is composite and multifaceted with several causes and risk factors responsible for different individual disease pathophysiological processes and clinical phenotypes. From a genetic and epigenetic side, several candidate genes have been reported as potentially linked to ASD, which can be detected in about 10-25% of patients. Folate gene polymorphisms have been previously associated with other psychiatric and neurodegenerative diseases, mainly focused on gene variants in the gene (5q14.1; rs70991108, 19bp ins/del), gene (1p36.22; rs1801133, C677T and rs1801131, A1298C), and gene (21q22.3; rs876657421, 844ins68). Of note, their roles have been scarcely investigated from a sex/gender viewpoint, though ASD is characterized by a strong sex gap in onset-risk and progression. The aim of the present review is to point out the molecular mechanisms related to intracellular folate recycling affecting in turn remethylation and transsulfuration pathways having potential effects on ASD. Brain epigenome during fetal life necessarily reflects the sex-dependent different imprint of the genome-environment interactions which effects are difficult to decrypt. We here will focus on the , and gene-triad by dissecting their roles in a sex-oriented view, primarily to bring new perspectives in ASD epigenetics.
自闭症谱系障碍（ASD）是一种复杂的神经发育障碍，影响行为和沟通，表现出极其不同的临床表型和特征。ASD 的病因是复合的和多方面的，有几个原因和风险因素导致不同个体的疾病病理生理过程和临床表型。从遗传和表观遗传方面来看，已经有几个候选基因被报道可能与 ASD 有关，这些基因可以在大约 10-25%的患者中检测到。叶酸基因多态性以前与其他精神和神经退行性疾病有关，主要集中在基因（5q14.1；rs70991108，19bp ins/del）、基因（1p36.22；rs1801133，C677T 和 rs1801131，A1298C）和基因（21q22.3；rs876657421，844ins68）的基因变异上。值得注意的是，尽管 ASD 在发病风险和进展方面存在明显的性别差距，但从性别角度来看，它们的作用几乎没有被研究过。本综述的目的是指出与细胞内叶酸循环有关的分子机制，这些机制反过来又影响再甲基化和转硫途径，从而对 ASD 产生潜在影响。胎儿期大脑表观基因组必然反映了基因组-环境相互作用的性别依赖性不同印记，这些影响很难解密。我们在这里将重点关注基因三重奏，通过从性别角度剖析它们的作用，为 ASD 表观遗传学带来新的视角。
