Child and Adolescent Neuropsychiatry Unit, University Campus Bio-Medico, Rome, Italy.
Behav Brain Res. 2013 Aug 15;251:95-112. doi: 10.1016/j.bbr.2013.06.012. Epub 2013 Jun 13.
Autism spectrum disorder (ASD) is a severe neuropsychiatric disease with strong genetic underpinnings. However, genetic contributions to autism are extremely heterogeneous, with many different loci underlying the disease to a different extent in different individuals. Moreover, the phenotypic expression (i.e., "penetrance") of these genetic components is also highly variable, ranging from fully penetrant point mutations to polygenic forms with multiple gene-gene and gene-environment interactions. Furthermore, many genes involved in ASD are also involved in intellectual disability, further underscoring their lack of specificity in phenotypic expression. We shall hereby review current knowledge on the genetic basis of ASD, spanning genetic/genomic syndromes associated with autism, monogenic forms due to copy number variants (CNVs) or rare point mutations, mitochondrial forms, and polygenic autisms. Finally, the recent contributions of genome-wide association and whole exome sequencing studies will be highlighted.
自闭症谱系障碍(ASD)是一种严重的神经精神疾病,具有很强的遗传基础。然而,自闭症的遗传贡献极其多样化,许多不同的基因座在不同个体中以不同的程度导致该疾病。此外,这些遗传成分的表型表达(即“外显率”)也高度可变,从完全外显的点突变到具有多种基因-基因和基因-环境相互作用的多基因形式。此外,许多与 ASD 相关的基因也与智力障碍有关,这进一步强调了它们在表型表达上缺乏特异性。我们将在此回顾 ASD 的遗传基础的现有知识,涵盖与自闭症相关的遗传/基因组综合征、由于拷贝数变异(CNV)或罕见点突变引起的单基因形式、线粒体形式和多基因自闭症。最后,将重点介绍全基因组关联和全外显子组测序研究的最新贡献。