Human Genetics and Cognitive Functions, Institut Pasteur, 75015 Paris, France.
Trends Genet. 2010 Aug;26(8):363-72. doi: 10.1016/j.tig.2010.05.007. Epub 2010 Jul 6.
Autism spectrum disorders (ASD) are characterized by impairments in reciprocal social communication, and repetitive, stereotyped verbal and non-verbal behaviors. Genetic studies have provided a relatively large number of genes that constitute a comprehensive framework to better understand this complex and heterogeneous syndrome. Based on the most robust findings, three observations can be made. First, genetic contributions to ASD are highly heterogeneous and most probably involve a combination of alleles with low and high penetrance. Second, the majority of the mutations apparently affect a single allele, suggesting a key role for gene dosage in susceptibility to ASD. Finally, the broad expression and function of the causative genes suggest that alteration of synaptic homeostasis could be a common biological process associated with ASD. Understanding the mechanisms that regulate synaptic homeostasis should shed new light on the causes of ASD and could provide a means to modulate the severity of the symptoms.
自闭症谱系障碍（ASD）的特征是在互惠社会交流方面存在障碍，以及重复性、刻板性的言语和非言语行为。遗传研究提供了相对大量的基因，这些基因构成了一个全面的框架，以更好地理解这种复杂和异质的综合征。基于最可靠的发现，可以得出三个观察结果。首先，ASD 的遗传贡献高度异质，很可能涉及低和高外显率等位基因的组合。其次，大多数突变显然只影响单个等位基因，这表明基因剂量在易感性方面起关键作用。最后，致病基因的广泛表达和功能表明，突触稳态的改变可能是与 ASD 相关的一个常见的生物学过程。了解调节突触稳态的机制应该能为 ASD 的病因提供新的认识，并为调节症状的严重程度提供一种手段。
