GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE126253 Query DataSets for GSE126253
Status Public on Feb 08, 2019
Title A pathogenic CtBP1 missense mutation causes altered cofactor binding and transcriptional activity
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary We previously reported a pathogenic de novo W342 mutation in the transcriptional corepressor CtBP1 in four independent patients with neurodevelopmental disabilities. Here, we report the clinical phenotypes of seven additional individuals with the same recurrent de novo CtBP1 mutation. Within this cohort we identified consistent CtBP1-related phenotypes of intellectual disability, ataxia, hypotonia and tooth enamel defects present in all patients. The W342 mutation in CtBP1 is located within a region implicated in a high affinity-binding cleft for CtBP-interacting proteins. Unbiased proteomic analysis demonstrated reduced interaction of several chromatin modifying factors with the CtBP1 W342 mutant. Genome-wide transcriptome analysis in human glioblastoma cells lines expressing -CtBP1 R342 (wt) or W342 mutation revealed changes in the expression profiles of genes controlling multiple cellular processes. Patient-derived dermal fibroblasts were found to be more sensitive to apoptosis during acute glucose deprivation compared to controls. Glucose deprivation strongly activated the BH3-only pro-apoptotic gene NOXA, suggesting a link between enhanced cell death and NOXA expression in patient fibroblasts. Our results suggest that context-dependent relief of transcriptional repression of the CtBP1 mutant W342 allele may contribute to deregulation of apoptosis in target tissues of patients leading to neurodevelopmental phenotypes.
Overall design Total RNA samples were isolated from 3 different cultures of HTB17 cells that overexpressed CtBP1 wt or the pathogenic mutant, W342 and analyzed by high- throughput RNA sequencing.
Contributor(s) Chinnadurai G, Subramanian T
Citation(s) 31041561
Submission date Feb 07, 2019
Last update date May 10, 2019
Contact name Govindaswamy Chinnadurai
Organization name Saint Louis University
Department Molecular Microbiology and Immunology
Street address 1100 South Grand Blvd
City St. Louis
State/province MO
ZIP/Postal code 63104
Country USA
Platforms (1)
GPL17303 Ion Torrent Proton (Homo sapiens)
Samples (6)
GSM3595392 HTB.CtBP.1
GSM3595393 HTB.CtBP.2
GSM3595394 HTB.CtBP.3
BioProject PRJNA521403
SRA SRP184530

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE126253_expression.xlsx 1.0 Mb (ftp)(http) XLSX
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap