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sequences from the largest collection of trios (5,947) with autism spectrum disorder (ASD) available, including 282 unpublished trios, and performed resequencing using multiple independent technologies.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：

---

自闭症谱系障碍中合子后嵌合突变的发生率、分布和影响。

我们系统地分析了最大的自闭症谱系障碍 (ASD) 三重奏 (5,947) 集合中全外显子组序列中的合子后突变 (PZM)，其中包括 282 个未发表的三重奏，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，其中 83.3% 未在之前的研究中描述。产前表达基因的关键外显子内的破坏性非同义 PZM 在 ASD 先证者中比对照组更常见（P < 1 × 10 ^-6），携带这些 PZM 的基因在杏仁核中的表达富集（P = 5.4 × 10 ^-3）。两个基因（KLF16 和 MSANTD2）在全基因组 PZM 中显着富集，其他 PZM 涉及的基因（SCN2A、HNRNPU 和 SMARCA4）已知其突变会导致 ASD 或其他神经发育障碍。PZM 占新生突变的很大一部分，并且对 ASD 风险有重要影响。