neurodevelopmental disorders
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2022 ◽  
Vol 122 ◽  
pp. 104166
Author(s):  
Victoria Perry ◽  
Katherine Ellis ◽  
Jo Moss ◽  
Sarah R. Beck ◽  
Gursharan Singla ◽  
...  

2022 ◽  
Author(s):  
Samuel Thudium ◽  
Katherine C Palozola ◽  
Eloise L'Her ◽  
Erica Korb

Epigenetic regulation plays a critical role in many neurodevelopmental disorders, including Autism Spectrum Disorder (ASD). In particular, many such disorders are the result of mutations in genes that encode chromatin modifying proteins. However, while these disorders share many features, it is unclear whether they also share gene expression disruptions resulting from the aberrant regulation of chromatin. We examined 5 chromatin modifiers that are all linked to ASD despite their different roles in regulating chromatin. Specifically, we depleted Ash1L, Chd8, Crebbp, Ehmt1, and Nsd1 in parallel in a highly controlled neuronal culture system. We then identified sets of shared genes, or transcriptional signatures, that are differentially expressed following loss of multiple ASD-linked chromatin modifiers. We examined the functions of genes within the transcriptional signatures and found an enrichment in many neurotransmitter transport genes and activity-dependent genes. In addition, these genes are enriched for specific chromatin features such as bivalent domains that allow for highly dynamic regulation of gene expression. The downregulated transcriptional signature is also observed within multiple mouse models of neurodevelopmental disorders that result in ASD, but not those only associated with intellectual disability. Finally, the downregulated transcriptional signature can distinguish between neurons generated from iPSCs derived from healthy donors and idiopathic ASD patients through RNA-deconvolution, demonstrating that this gene set is relevant to the human disorder. This work identifies a transcriptional signature that is found within many neurodevelopmental syndromes, helping to elucidate the link between epigenetic regulation and the underlying cellular mechanisms that result in ASD.


Genes ◽  
2022 ◽  
Vol 13 (1) ◽  
pp. 154
Author(s):  
Dóra Nagy ◽  
Sarah Verheyen ◽  
Kristen M. Wigby ◽  
Artem Borovikov ◽  
Artem Sharkov ◽  
...  

POGZ-related disorders (also known as White-Sutton syndrome) encompass a wide range of neurocognitive abnormalities and other accompanying anomalies. Disease severity varies widely among POGZ patients and studies investigating genotype-phenotype association are scarce. Therefore, our aim was to collect data on previously unreported POGZ patients and perform a large-scale phenotype-genotype comparison from published data. Overall, 117 POGZ patients′ genotype and phenotype data were included in the analysis, including 12 novel patients. A severity scoring system was developed for the comparison. Mild and severe phenotypes were compared with the types and location of the variants and the predicted presence or absence of nonsense-mediated RNA decay (NMD). Missense variants were more often associated with mild phenotypes (p = 0.0421) and truncating variants predicted to escape NMD presented with more severe phenotypes (p < 0.0001). Within this group, variants in the prolin-rich region of the POGZ protein were associated with the most severe phenotypes (p = 0.0004). Our study suggests that gain-of-function or dominant negative effect through escaping NMD and the location of the variants in the prolin-rich domain of the protein may play an important role in the severity of manifestations of POGZ–associated neurodevelopmental disorders.


2022 ◽  
Vol 8 (2) ◽  
Author(s):  
Ruth Nussinov ◽  
Chung-Jung Tsai ◽  
Hyunbum Jang

This review offers why same-gene mutations can lead to cancer and neurodevelopmental disorders and why a high risk of cancer.


Author(s):  
Laura E.R. Blok ◽  
Marina Boon ◽  
Boyd van Reijmersdal ◽  
Kira D. Höffler ◽  
Michaela Fenckova ◽  
...  

Habituation, the most ancient and fundamental form of learning, manifests already before birth. Neuroscientists have been fascinated for decades by its function as a firewall protecting our brains from sensory information overload and its indispensability for higher cognitive processing. Evidence that habituation learning is affected in autism and related monogenic neurodevelopmental syndromes and their animal models has exponentially grown, but the potential of this convergence to advance both fields is still largely unexploited.In this review, we provide a systematic overview of the genes that to date have been demonstrated to underlie habituation across species. We describe the biological processes they converge on, and highlight core regulatory pathways and repurposable drugs that may alleviate the habituation deficits associated with their dysregulation. We also summarize currently used habituation paradigms and extract the most important arguments from literature that support the crucial role of habituation for cognition in health and disease. We conclude that habituation is a powerful tool to overcome current bottlenecks in research, diagnostics and treatment of neurodevelopmental disorders.


Author(s):  
Mahdiyeh Moudi ◽  
Mohammad Yahya Vahidi Mehrjardi ◽  
Hossein Hozhabri ◽  
Zahra Metanat ◽  
Seyed Mehdi Kalantar ◽  
...  

2022 ◽  
Author(s):  
Brett Steven Gunn ◽  
Thomas McAllister ◽  
Michael McCrea ◽  
Steven P Broglio ◽  
R. Davis Moore

JCI Insight ◽  
2022 ◽  
Vol 7 (1) ◽  
Author(s):  
Yue-Peng Zhou ◽  
Meng-Jie Mei ◽  
Xian-Zhang Wang ◽  
Sheng-Nan Huang ◽  
Lin Chen ◽  
...  

Author(s):  
Else Marie Olsen ◽  
Charlotte M. Wright ◽  
Kim Fleischer Michaelsen ◽  
Kristine Kahr Nilsson ◽  
Anne Mette Skovgaard

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