Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder

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sequences from the largest collection of trios (5,947) with autism spectrum disorder (ASD) available, including 282 unpublished trios, and performed resequencing using multiple independent technologies.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 Ã 10-6), and genes carrying these PZMs were enriched for expression in the amygdala (P = 5.4 Ã 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

Rates, Distribution, and Implications of Post-zygotic Mosaic Mutations in Autism Spectrum Disorder

We systematically analyzed post-zygotic 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sequences from the largest collection of trios (5,947) with autism spectrum disorder (ASD) available, including 282 unpublished trios, and performed re-sequencing using multiple independent technologies. We identified 7.5% of de novo mutations as PZMs, with 83.3% of these PZMs not discovered in previous studies. Damaging, non-synonymous 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, SMARCA4) known to cause ASD or other neurodevelopmental disorders. PZMs constitute a significant proportion of de novo mutations and contribute importantly to ASD risk

Publisher Correction: Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Publisher Correction: Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder

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 7 10-6), and genes carrying these PZMs were enriched for expression in the amygdala (P = 5.4 7 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