Chromatin Remodeler CHD8 in Autism and Brain Development

Hoffmann, Anke; Spengler, Dietmar

doi:10.3390/jcm10020366

Cited by 23 publications

(11 citation statements)

References 83 publications

(158 reference statements)

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“…Besides the SCN2A , FOXP1 , and SYNGAP1 genes, CHD8 variants are among the most replicated and common findings in ASD genetic studies. They are associated with the most common form of autism spectrum disorder, classic autism, along with macrocephaly, distinct dysmorphic facial features, and gastrointestinal disturbance [ 20 , 21 ]. Genetic variants in the SCN2A gene are also important in ASD; they can play a significant role in psychiatric disorders.…”

Section: Discussionmentioning

confidence: 99%

Exome Evaluation of Autism-Associated Genes in Amazon American Populations

Costa

Fernandes

Rodrigues

et al. 2022

Genes

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Autism spectrum disorder is a neurodevelopmental disorder, affecting one in 160 children worldwide. The causes of autism are still poorly understood, but research shows the relevance of genetic factors in its pathophysiology, including the CHD8, SCN2A, FOXP1 and SYNGAP1 genes. Information about the genetic influence on various diseases, including autism, in the Amerindian population from Amazon, is still scarce. We investigated 35 variants of the CHD8, SCN2A, FOXP1, and SYNGAP1 gene in Amazonian Amerindians in comparison with publicly available population frequencies from the 1000 Genomes Project database. Our study identified 16 variants in the Amerindian population of the Amazon with frequencies significantly different from the other populations. Among them, the SCN2A (rs17183814, rs75109281, and rs150453735), FOXP1 (rs56850311 and rs939845), and SYNGAP1 (rs9394145 and rs115441992) variants presented higher frequency than all other populations analyzed. In addition, nine variants were found with lower frequency among the Amerindians: CHD8 (rs35057134 and rs10467770), SCN2A (rs3769951, rs2304014, rs1838846, and rs7593568), FOXP1 (rs112773801 and rs56850311), and SYNGAP1 (rs453590). These data show the unique genetic profile of the indigenous population of the Brazilian Amazon. Knowledge of these variants can help to understand the pathophysiology and diagnosis of autism among Amerindians, Brazilians, and in admixed populations that have contributions from this ethnic group.

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Section: Discussionmentioning

confidence: 99%

Exome Evaluation of Autism-Associated Genes in Amazon American Populations

Costa

Fernandes

Rodrigues

et al. 2022

Genes

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“…Established Mecp2 and Chd8 genetic mouse models exist that display ASD-related behavioral phenotypes such as altered sensory responses as well as showing synaptic and brain connectivity deficits [ 39 , 59 , 78 , 92 , 93 ]. Aligned with the synaptic genes discussed in this review, these genes are specifically important during embryonic and early postnatal development in cortico-striatal neuronal circuits; recently, these topics have been elegantly described in detail for Mecp2 and Chd8 by Hoffmann and Spengler et al, 2021; Li and Pozzo-Miller, 2020; Smith et al, 2019, and Varghese et al, 2017 [ 94 , 95 , 96 , 97 ].…”

Section: From Neural Circuit To Targeted Gene-based Therapymentioning

confidence: 99%

Spatial and Temporal Gene Function Studies in Rodents: Towards Gene-Based Therapies for Autism Spectrum Disorder

Riemersma

Havekes

Kas

2021

Genes

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Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that is characterized by differences in social interaction, repetitive behaviors, restricted interests, and sensory differences beginning early in life. Especially sensory symptoms are highly correlated with the severity of other behavioral differences. ASD is a highly heterogeneous condition on multiple levels, including clinical presentation, genetics, and developmental trajectories. Over a thousand genes have been implicated in ASD. This has facilitated the generation of more than two hundred genetic mouse models that are contributing to understanding the biological underpinnings of ASD. Since the first symptoms already arise during early life, it is especially important to identify both spatial and temporal gene functions in relation to the ASD phenotype. To further decompose the heterogeneity, ASD-related genes can be divided into different subgroups based on common functions, such as genes involved in synaptic function. Furthermore, finding common biological processes that are modulated by this subgroup of genes is essential for possible patient stratification and the development of personalized early treatments. Here, we review the current knowledge on behavioral rodent models of synaptic dysfunction by focusing on behavioral phenotypes, spatial and temporal gene function, and molecular targets that could lead to new targeted gene-based therapy.

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“…Using the SFARI gene database, 212 genes—environment interacting pairs—have been identified [ 82 , 83 ]. Some examples of the genes associated with autism include MECP2, CHD8, KMT2A, GRIN2B, SCN2A, NLGN1, NLGN3, MET, CNTNAP2, FOXP2, TSHZ3, SHANK3, PTEN, DYRK1A, RELN, FOXP1, SYNGAP1, NRXN [ 84 , 85 ], the NLGN gene series (NLGN1, NLGN2, NLGN4, and NLGN4Y) [ 86 , 87 ], brain function protein-related genes (such as GABRA5, GABRB3, UBE3A, HERC2 and CYFIP1 [ 88 ]), NRXN2, POGZ, RFX3, ANK2, ARHGEF10, BRD3, CEP152, CHRM3 [ 89 ], STX1A, NLGN3, SHANK2, DLGAP1, NRXN3, DLG4, CACNG2, AKAP9, CACNA1C, KCNS3, CACNA2D3 [ 90 ], and some metabolic genes, (such as GSTT1, GSTM1, and GSTP1 [ 91 ]). Many of these genes are pleiotropic in nature [ 92 ].…”

Section: Genes and Geneticsmentioning

confidence: 99%

Symptomatic, Genetic, and Mechanistic Overlaps between Autism and Alzheimer’s Disease

et al. 2021

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Autism spectrum disorder (ASD) and Alzheimer’s disease (AD) are neurodevelopmental and neurodegenerative disorders affecting two opposite ends of life span, i.e., childhood and old age. Both disorders pose a cumulative threat to human health, with the rate of incidences increasing considerably worldwide. In the context of recent developments, we aimed to review correlated symptoms and genetics, and overlapping aspects in the mechanisms of the pathogenesis of ASD and AD. Dementia, insomnia, and weak neuromuscular interaction, as well as communicative and cognitive impairments, are shared symptoms. A number of genes and proteins linked with both disorders have been tabulated, including MECP2, ADNP, SCN2A, NLGN, SHANK, PTEN, RELN, and FMR1. Theories about the role of neuron development, processing, connectivity, and levels of neurotransmitters in both disorders have been discussed. Based on the recent literature, the roles of FMRP (Fragile X mental retardation protein), hnRNPC (heterogeneous ribonucleoprotein-C), IRP (Iron regulatory proteins), miRNAs (MicroRNAs), and α-, β0, and γ-secretases in the posttranscriptional regulation of cellular synthesis and processing of APP (amyloid-β precursor protein) have been elaborated to describe the parallel and overlapping routes and mechanisms of ASD and AD pathogenesis. However, the interactive role of genetic and environmental factors, oxidative and metal ion stress, mutations in the associated genes, and alterations in the related cellular pathways in the development of ASD and AD needs further investigation.

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Chromatin Remodeler CHD8 in Autism and Brain Development

Cited by 23 publications

References 83 publications

Exome Evaluation of Autism-Associated Genes in Amazon American Populations

Exome Evaluation of Autism-Associated Genes in Amazon American Populations

Spatial and Temporal Gene Function Studies in Rodents: Towards Gene-Based Therapies for Autism Spectrum Disorder

Symptomatic, Genetic, and Mechanistic Overlaps between Autism and Alzheimer’s Disease

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