Ayhan Fatma, Konopka Genevieve
Department of Neuroscience, UT Southwestern Medical Center, Dallas, 75390-9111 TX, USA.
F1000Res. 2018 May 22;7. doi: 10.12688/f1000research.13865.1. eCollection 2018.
Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental condition with no current treatment available. Although advances in genetics and genomics have identified hundreds of genes associated with ASD, very little is known about the pathophysiology of ASD and the functional contribution of specific genes to ASD phenotypes. Improved understanding of the biological function of ASD-associated genes and how this heterogeneous group of genetic variants leads to the disease is needed in order to develop therapeutic strategies. Here, we review the current state of ASD research related to gene discovery and examples of emerging molecular mechanisms (protein translation and alternative splicing). In addition, we discuss how patient-derived three-dimensional brain organoids might provide an opportunity to model specific genetic variants in order to define molecular and cellular defects that could be amenable for developing and screening personalized therapies related to ASD.
自闭症谱系障碍（ASD）是一种高度普遍的神经发育疾病，目前尚无有效治疗方法。尽管遗传学和基因组学的进展已鉴定出数百个与ASD相关的基因，但对于ASD的病理生理学以及特定基因对ASD表型的功能贡献却知之甚少。为了制定治疗策略，需要更好地了解与ASD相关基因的生物学功能以及这一异质性基因变异群体如何导致该疾病。在此，我们综述了与基因发现相关的ASD研究现状以及新兴分子机制（蛋白质翻译和可变剪接）的实例。此外，我们还讨论了患者来源的三维脑类器官如何可能提供一个机会来模拟特定的基因变异，以便确定那些适合开发和筛选与ASD相关的个性化疗法的分子和细胞缺陷。
