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| Status |
Public on Jul 27, 2020 |
| Title |
Presynaptic dysfunction in CASK-related neurodevelopmental disorders |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
CASK-related disorders are a growing group of genetic neurodevelopmental syndromes. There is limited information about the effects of CASK mutations in human neurons. Therefore, we sought to delineate CASK mutation consequences and neuronal level effects using induced pluripotent stem cell-derived neurons from two mutation carriers; one male diagnosed with ASD and a female with MICPCH. We show a reduction of the CASK protein in maturing neurons from the mutation carriers, which leads to significant downregulation of gene sets involved in presynaptic development and CASK protein interactors. Furthermore, CASK-deficient neurons showed decreased inhibitory presynapse size as indicated by VGAT stainings, which may alter E/I balance in developing neural circuitries. Using in vivo magnetic resonance spectroscopy quantification of GABA in the male mutation carrier, we further highlight the possibility to validate in vitro cellular data in brain. Our data shows that future pharmacological and clinical studies on targeting presynapses and E/I imbalance could lead to specific treatments for CASK-related disorders.
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| Overall design |
Transcriptomes of two case and two control iPSC derived neuronal cultures were sequenced in quintuplicate
***The submitters are not legally permitted to submit the raw data to GEO or a restricted-access database such as dbGaP or EGA. Therefore, raw data is not provided.
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| Contributor(s) |
Becker M, Mastropasqua F, Reising JP, Maier S, Ho M, Rabkina I, Li D, Neufeld J, Ballenberger L, Myers L, Moritz V, Kele M, Wincent J, Willfors C, Sitnikov R, Herlenius E, Anderlid B, Falk A, Bölte S, Tammimies K |
| Citation(s) |
32929080 |
| Submission date |
Nov 18, 2019 |
| Last update date |
Oct 26, 2020 |
| Contact name |
Martin Becker |
| Organization name |
Karolinska Institutet
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| Department |
Department of Women's and Children's Health
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| Lab |
Tammimies Lab
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| Street address |
Akademiska stråket 1
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| City |
Solna |
| ZIP/Postal code |
17164 |
| Country |
Sweden |
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| Platforms (2) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA590196 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE140572_RAW.tar |
6.0 Mb |
(http)(custom) |
TAR (of TXT) |
| Raw data not provided for this record |
| Processed data provided as supplementary file |
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