Despite evidence that deleterious variants in the same genes are implicated across multiple neurodevelopmental and neuropsychiatric disorders, there has been considerable interest in identifying genes that, when mutated, confer risk that is largely specific for autism spectrum disorder (ASD). Here, we review the findings and limitations of recent efforts to identify relatively "autism-specific" genes, efforts which focus on rare variants of large effect size that are thought to account for the observed phenotypes. We present a divergent interpretation of published evidence; discuss practical and theoretical issues related to studying the relationships between rare, large-effect deleterious variants and neurodevelopmental phenotypes; and describe potential future directions of this research. We argue that there is currently insufficient evidence to establish meaningful ASD specificity of any genes based on large-effect rare-variant data.

中文翻译：

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“自闭症相关”基因的证据不足。

尽管有证据表明同一基因中的有害变异涉及多种神经发育和神经精神疾病，但人们对鉴定基因产生了浓厚的兴趣，这些基因突变后会带来自闭症谱系障碍（ASD）特有的风险。在这里，我们回顾了鉴定相对“自闭症特异性”基因的最新成果的发现和局限性，这些成果集中于被认为是所观察到表型的大效应大小的罕见变异。我们对已发表的证据有不同的解释；讨论与研究稀有的，有效的有害变异与神经发育表型之间的关系有关的实践和理论问题；并描述这项研究的潜在未来方向。