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Series GSE140572 Query DataSets for GSE140572
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
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.
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.
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
Department Department of Women's and Children's Health
Lab Tammimies Lab
Street address Akademiska stråket 1
City Solna
ZIP/Postal code 17164
Country Sweden
Platforms (2)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (3)
GSM4174612 scRNA-Seq MICPCH-CASKdup45
GSM4174613 bulkRNA-Seq of cases and controls
GSM4174614 bulkRNA-Seq of siRNA KD
BioProject PRJNA590196

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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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