Yasuda Yuka, Matsumoto Junya, Miura Kenichiro, Hasegawa Naomi, Hashimoto Ryota
Life Grow Blliliant Mental Clinic, Medical Corporation Foster, Osaka, Japan.
Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Japan.
J Hum Genet. 2023 Mar;68(3):193-197. doi: 10.1038/s10038-022-01076-3. Epub 2022 Aug 30.
Autism spectrum disorders (ASDs) have been increasing in prevalence. ASD is a complex human genetic disorder with high heredity and involves interactions between genes and the environment. A significant inheritance pattern in ASD involves a rare genetic mutation; common copy number variants refer to duplication or deletion of stretches of chromosomal loci or protein-disrupting single-nucleotide variants. Haploinsufficiency is one of the more common single-gene causes of ASD, explaining at least 0.5% of cases. Epigenetic mechanisms, such as DNA methylation, act at an interface of genetic and environmental risk and protective factors. Advances in genome-wide sequencing have broadened the view of the human methylome and have revealed the organization of the human genome into large-scale methylation domains with a footprint over neurologically important genes involved in embryonic development. Psychiatric disorders, including ASD, are expected to be diagnosed based on their genetically regulated pathophysiology and to be linked to their treatment.
自闭症谱系障碍（ASD）的患病率一直在上升。ASD是一种具有高遗传性的复杂人类遗传疾病，涉及基因与环境之间的相互作用。ASD中一种重要的遗传模式涉及罕见的基因突变；常见的拷贝数变异是指染色体位点片段的重复或缺失或破坏蛋白质的单核苷酸变异。单倍体不足是ASD较常见的单基因病因之一，至少解释了0.5%的病例。表观遗传机制，如DNA甲基化，作用于遗传和环境风险及保护因素的界面。全基因组测序的进展拓宽了对人类甲基化组的认识，并揭示了人类基因组被组织成大规模甲基化结构域，其足迹覆盖了参与胚胎发育的对神经功能重要的基因。包括ASD在内的精神疾病有望根据其基因调控的病理生理学进行诊断，并与治疗相关联。
