Genetics and epigenetics of autism: A Review

Waye, Mary Miu Yee; Cheng, Ho Yu

doi:10.1111/pcn.12606

Cited by 111 publications

(60 citation statements)

References 150 publications

(278 reference statements)

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“…Considering that POGZ is suggested to form part of a nuclear complex with CHD4 as well as SP1 and HP1 35,36,47 , POGZ is likely to regulate transcriptional networks controlling neuronal differentiation through chromatin remodeling.…”

Section: Discussionmentioning

confidence: 99%

Pathogenic POGZ mutation causes impaired cortical development and reversible autism-like phenotypes

et al. 2020

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Pogo transposable element derived with ZNF domain (POGZ) has been identified as one of the most recurrently de novo mutated genes in patients with neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), intellectual disability and White-Sutton syndrome; however, the neurobiological basis behind these disorders remains unknown. Here, we show that POGZ regulates neuronal development and that ASD-related de novo mutations impair neuronal development in the developing mouse brain and induced pluripotent cell lines from an ASD patient. We also develop the first mouse model heterozygous for a de novo POGZ mutation identified in a patient with ASD, and we identify ASD-like abnormalities in the mice. Importantly, social deficits can be treated by compensatory inhibition of elevated cell excitability in the mice. Our results provide insight into how de novo mutations on high-confidence ASD genes lead to impaired mature cortical network function, which underlies the cellular pathogenesis of NDDs, including ASD.

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Section: Discussionmentioning

confidence: 99%

Pathogenic POGZ mutation causes impaired cortical development and reversible autism-like phenotypes

et al. 2020

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“…In addition to the genetic factors, environmental and/or immune factors contribute to the risk of autism during early life (Waye and Cheng, 2018). The interaction of environmental exposures with an individual genetic background and particular susceptibility manifests differently in each case, leading to heterogeneous phenotypes and varied comorbid symptoms within the disorder.…”

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confidence: 99%

A Synaptic Perspective of Fragile X Syndrome and Autism Spectrum Disorders

Bagni

Zukin

2019

Neuron

235

258

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Altered synaptic structure and function is a major hallmark of fragile X syndrome (FXS), autism spectrum disorders (ASDs), and other intellectual disabilities (IDs), which are therefore classified as synaptopathies. FXS and ASDs, while clinically and genetically distinct, share significant comorbidity, suggesting that there may be a common molecular and/or cellular basis, presumably at the synapse. In this article, we review brain architecture and synaptic pathways that are dysregulated in FXS and ASDs, including spine architecture, signaling in synaptic plasticity, local protein synthesis, (m)RNA modifications, and degradation. mRNA repression is a powerful mechanism for the regulation of synaptic structure and efficacy. We infer that there is no single pathway that explains most of the etiology and discuss new findings and the implications for future work directed at improving our understanding of the pathogenesis of FXS and related ASDs and the design of therapeutic strategies to ameliorate these disorders. ASDs and FXS: Causes and Clinical Features Approximately 1%-3% of the general population is affected by intellectual disabilities (IDs). IDs are neurodevelopmental disorders defined by significant limitations in intellectual functioning and adaptive behaviors and often exhibit comorbidity with autism (Mefford et al., 2012). Autism spectrum disorders (ASDs) are characterized by high phenotypic heterogeneity, comprising deficits in social interaction and communication as well as repetitive and stereotyped behaviors (

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“…Although autism spectrum disorder (ASD) and type 1 diabetes (T1D) are conditions both encountered in pediatric patients, their co‐existence has not been well characterized. ASD has been the subject of increasing attention over the last decade and its potential cause remains undetermined; however, studies often report changes in default mode network connectivity and high heritability . The global prevalence of ASD is increasing worldwide with approximately 1 in 68 children in the United States diagnosed with ASD .…”

Section: Introductionmentioning

confidence: 99%