We systematically analyzed postzygotic mutations (PZMs) in whole-exome sequences from the largest collection of trios (5,947) with autism spectrum disorder (ASD) available, including 282 unpublished trios, and performed resequencing using multiple independent technologies. We identified 7.5% of de novo mutations as PZMs, 83.3% of which were not described in previous studies. Damaging, nonsynonymous PZMs within critical exons of prenatally expressed genes were more common in ASD probands than controls (P < 1 × 10⁻⁶), and genes carrying these PZMs were enriched for expression in the amygdala (P = 5.4 × 10⁻³). Two genes (KLF16 and MSANTD2) were significantly enriched for PZMs genome-wide, and other PZMs involved genes (SCN2A, HNRNPU and SMARCA4) whose mutation is known to cause ASD or other neurodevelopmental disorders. PZMs constitute a significant proportion of de novo mutations and contribute importantly to ASD risk.

中文翻译：

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自闭症谱系障碍的合子后镶嵌突变的发生率，分布及意义

我们系统地分析了来自最大的三重奏（5,947）自闭症谱系障碍（ASD）包括282个未发表的三重奏的三重奏的全外显子序列中的合子后突变（PZMs），并使用多种独立技术进行了重测序。我们确定了7.5％的从头突变为PZM，先前的研究中未描述其中的83.3％。在ASD先证者中，产前表达基因的关键外显子中的破坏性，非同义PZM比对照组更为常见（P <1×10 ^-6），携带这些PZM的基因在杏仁核中表达丰富（P = 5.4×10 ^-3）。 。两个基因（KLF16和MSANTD2）显着富集了全基因组中的PZM，其他PZM涉及的基因（SCN2A，HNRNPU和SMARCA4）的基因突变已知会引起ASD或其他神经发育障碍。PZM构成了从头突变的重要部分，并且对ASD风险起重要作用。