CHD2-Related CNS Pathologies

Wilson, Marc-Michel; Henshall, David C.; Byrne, Susan; Brennan, Gary P.

doi:10.3390/ijms22020588

Cited by 21 publications

(18 citation statements)

References 127 publications

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“…It encodes a member of the chromodomain helicase DNA-binding (CHD) family of proteins, of which the canonical function is the gene expression regulation by epigenetic changes in chromatin [ 52 ]. Loss of function of CHD2 is identified as a cause of developmental epileptic encephalopathy (DEE) [ 52 ], being associated with childhood-onset epileptic encephalopathy (EEOC; MIM #615369) and MAE (ORPHA 1942) [ 53 , 54 ]. Usually, it is also characterized by cognitive regression, ID, ASD-like phenotype, and resistance to antiepileptic drugs (AED) treatment [ 52 ].…”

Section: Resultsmentioning

confidence: 99%

“…Loss of function of CHD2 is identified as a cause of developmental epileptic encephalopathy (DEE) [ 52 ], being associated with childhood-onset epileptic encephalopathy (EEOC; MIM #615369) and MAE (ORPHA 1942) [ 53 , 54 ]. Usually, it is also characterized by cognitive regression, ID, ASD-like phenotype, and resistance to antiepileptic drugs (AED) treatment [ 52 ].…”

Section: Resultsmentioning

confidence: 99%

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Candidate Genes for Eyelid Myoclonia with Absences, Review of the Literature

Mayo

Gómez-Manjón

Fernández-Martínez

et al. 2021

IJMS

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Eyelid myoclonia with absences (EMA), also known as Jeavons syndrome (JS) is a childhood onset epileptic syndrome with manifestations involving a clinical triad of absence seizures with eyelid myoclonia (EM), photosensitivity (PS), and seizures or electroencephalogram (EEG) paroxysms induced by eye closure. Although a genetic contribution to this syndrome is likely and some genetic alterations have been defined in several cases, the genes responsible for have not been identified. In this review, patients diagnosed with EMA (or EMA-like phenotype) with a genetic diagnosis are summarized. Based on this, four genes could be associated to this syndrome (SYNGAP1, KIA02022/NEXMIF, RORB, and CHD2). Moreover, although there is not enough evidence yet to consider them as candidate for EMA, three more genes present also different alterations in some patients with clinical diagnosis of the disease (SLC2A1, NAA10, and KCNB1). Therefore, a possible relationship of these genes with the disease is discussed in this review.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Candidate Genes for Eyelid Myoclonia with Absences, Review of the Literature

Mayo

Gómez-Manjón

Fernández-Martínez

et al. 2021

IJMS

View full text Add to dashboard Cite

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“…CHD2 belongs to the chromodomain helicase DNA binding families of chromatin remodeling proteins, and haplo-insufficiency of this gene has been associated with a developmental and epileptic encephalopathy, presenting with early onset intractable seizures, cognitive regression, intellectual disability and ASD behaviors (OMIM #615369) [91]. Around 80 kb upstream of CHD2, we found a DAE that interacts with the CHD2 promoter (Figure 6A).…”

Section: Crispri and Zebrafish Experiments Confirm Enhancer Activity Of Daes Regulating Genes Involved In Epileptic Encephalopathymentioning

confidence: 89%

Comprehensive multi-omics integration identifies differentially active enhancers during human brain development with clinical relevance

Yousefi

Deng

Lanko

et al. 2021

Preprint

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Background: Non-coding regulatory elements (NCREs), such as enhancers, play a crucial role in gene regulation and genetic aberrations in NCREs can lead to human disease, including brain disorders. The human brain is complex and can be affected by numerous disorders; many of these are caused by genetic changes, but a multitude remain currently unexplained. Understanding NCREs acting during brain development has the potential to shed light on previously unrecognised genetic causes of human brain disease. Despite immense community-wide efforts to understand the role of the non-coding genome and NCREs, annotating functional NCREs remains challenging. Results: Here we performed an integrative computational analysis of virtually all currently available epigenome data sets related to human fetal brain. Our in-depth analysis unravels 39,709 differentially active enhancers (DAEs) that show dynamic epigenomic rearrangement during early stages of human brain development, indicating likely biological function. Many of these DAEs are linked to clinically relevant genes, and functional validation of selected DAEs in cell models and zebrafish confirms their role in gene regulation. Compared to enhancers without dynamic epigenomic rearrangement, these regions are subjected to higher sequence constraints in humans, have distinct sequence characteristics and are bound by a distinct transcription factor landscape. DAEs are enriched for GWAS loci for brain related traits and for genetic variation found in individuals with neurodevelopmental disorders, including autism. Conclusion: Our compendium of high-confidence enhancers will assist in deciphering the mechanism behind developmental genetics of the human brain and will be relevant to uncover missing heritability in human genetic brain disorders.

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“…Of the seven DMRs three were annotated to the regulatory regions of genes previously associated with neuropsychiatric disorders (SDK1, CHD2 and CLN8). SDK1 (The Sidekick Cell Adhesion Molecule 1) has been associated with ASD [21][22][23][24], and ADHD [25,26]; CHD2 (Chromodomain Helicase DNA Binding Protein 2) variants has been identified in individuals with central nervous system pathologies [27]; and CLN8 (the ceroid-lipofuscinosis, neuronal 8) has been linked to ASD through rare missense variants found in a Japanese family [28].…”

Section: Discussionmentioning

confidence: 99%

EWAS of Monozygotic Twins Implicate a Role of mTOR Pathway in Pathogenesis of Tic Spectrum Disorder

Hildonen

Levy

Hansen

et al. 2021

Genes

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Tic spectrum disorder (TSD) is an umbrella term which includes Gilles de la Tourette syndrome (GTS) and chronic tic disorder (CTD). They are considered highly heritable, yet the genetic components remain largely unknown. In this study we aimed to investigate disease-associated DNA methylation differences to identify genes and pathways which may be implicated in TSD aetiology. For this purpose, we performed an exploratory analysis of the genome-wide DNA methylation patterns in whole blood samples of 16 monozygotic twin pairs, of which eight were discordant and six concordant for TSD, while two pairs were asymptomatic. Although no sites reached genome-wide significance, we identified several sites and regions with a suggestive significance, which were located within or in the vicinity of genes with biological functions associated with neuropsychiatric disorders. The two top genes identified (TSC1 and CRYZ/TYW3) and the enriched pathways and components (phosphoinosides and PTEN pathways, and insulin receptor substrate binding) are related to, or have been associated with, the PI3K/AKT/mTOR pathway. Genes in this pathway have previously been associated with GTS, and mTOR signalling has been implicated in a range of neuropsychiatric disorders. It is thus possible that altered mTOR signalling plays a role in the complex pathogenesis of TSD.

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CHD2-Related CNS Pathologies

Cited by 21 publications

References 127 publications

Candidate Genes for Eyelid Myoclonia with Absences, Review of the Literature

Candidate Genes for Eyelid Myoclonia with Absences, Review of the Literature

Comprehensive multi-omics integration identifies differentially active enhancers during human brain development with clinical relevance

EWAS of Monozygotic Twins Implicate a Role of mTOR Pathway in Pathogenesis of Tic Spectrum Disorder

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