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| Status |
Public on Sep 14, 2020 |
| Title |
Distinct Pathogenic Genes Causing Intellectual Disability and Autism Exhibit a Common Neuronal Network Hyperactivity Phenotype |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Pathogenic mutations in either one of the epigenetic modifiers EHMT1, MBD5, MLL3, or SMARCB1 have been identified to be causative for Kleefstra syndrome spectrum (KSS), a neurodevelopmental disorder with clinical features of both intellectual disability (ID) and autism spectrum disorder (ASD). To understand how these variants lead to the phenotypic convergence in KSS, we employ a loss-of-function approach to assess neuronal network development at the molecular, single-cell, and network activity level. KSS-gene-deficient neuronal networks all develop into hyperactive networks with altered network organization and excitatory-inhibitory balance. Interestingly, even though transcriptional data reveal distinct regulatory mechanisms, KSS target genes share similar functions in regulating neuronal excitability and synaptic function, several of which are associated with ID and ASD. Our results show that KSS genes mainly converge at the level of neuronal network communication, providing insights into the pathophysiology of KSS and phenotypically congruent disorders.
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| Overall design |
Gene expression analysis in cotrtical neurons in which Kleeftrsa syndome genes have been downregulated
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| Contributor(s) |
Kasri NN, Zhou H |
| Citation(s) |
31914384 |
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| Submission date |
Sep 17, 2018 |
| Last update date |
Jun 14, 2022 |
| Contact name |
Jo Huiqing Zhou |
| E-mail(s) |
jo.zhou@radboudumc.nl
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| Organization name |
Radboud University
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| Street address |
Geert Grooteplein 26/28
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| City |
Nijmegen |
| ZIP/Postal code |
6525GA |
| Country |
Netherlands |
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| Platforms (1) |
| GPL20084 |
Illumina NextSeq 500 (Rattus norvegicus) |
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| Samples (5)
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| Relations |
| BioProject |
PRJNA491497 |
| SRA |
SRP161926 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE120061_GFP_vs_Ehmt1.txt.gz |
789.7 Kb |
(ftp)(http) |
TXT |
| GSE120061_GFP_vs_Mbd5.txt.gz |
819.8 Kb |
(ftp)(http) |
TXT |
| GSE120061_GFP_vs_Mll3.txt.gz |
818.3 Kb |
(ftp)(http) |
TXT |
| GSE120061_GFP_vs_Smarcb1.txt.gz |
814.5 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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