Statistics Department, The Wharton School, University of Pennsylvania, Philadelphia, PA 19104.
Simons Foundation, New York, NY 10010.
Proc Natl Acad Sci U S A. 2018 Feb 20;115(8):E1859-E1866. doi: 10.1073/pnas.1715427115. Epub 2018 Feb 6.
In individuals with autism spectrum disorder (ASD), de novo mutations have previously been shown to be significantly correlated with lower IQ but not with the core characteristics of ASD: deficits in social communication and interaction and restricted interests and repetitive patterns of behavior. We extend these findings by demonstrating in the Simons Simplex Collection that damaging de novo mutations in ASD individuals are also significantly and convincingly correlated with measures of impaired motor skills. This correlation is not explained by a correlation between IQ and motor skills. We find that IQ and motor skills are distinctly associated with damaging mutations and, in particular, that motor skills are a more sensitive indicator of mutational severity than is IQ, as judged by mutational type and target gene. We use this finding to propose a combined classification of phenotypic severity: mild (little impairment of either), moderate (impairment mainly to motor skills), and severe (impairment of both IQ and motor skills).
在自闭症谱系障碍（ASD）患者中，先前已经表明新生突变与较低的智商显著相关，但与 ASD 的核心特征（社交沟通和互动方面的缺陷，以及受限的兴趣和重复行为模式）无关。我们通过在西蒙斯单倍型集合中证明，ASD 患者的破坏性新生突变也与运动技能受损的测量结果显著且令人信服地相关，从而扩展了这些发现。这种相关性不能用智商和运动技能之间的相关性来解释。我们发现智商和运动技能与破坏性突变明显相关，特别是运动技能比智商更能敏感地反映突变的严重程度，这可以通过突变类型和靶基因来判断。我们利用这一发现提出了一种综合的表型严重程度分类：轻度（两者均无明显受损）、中度（主要是运动技能受损）和重度（智商和运动技能均受损）。
