GEO DataSets

(Submitter supplied) Epigenetic dysregulation has emerged as mechanism in the etiology of neurodevelopmental disorders. Two such disorders, CHARGE and Kabuki syndromes, result from loss of function mutations in chromodomain helicase DNA-binding protein 7 (CHD7LOF) and lysine (K) methyltransferase 2D (KMT2DLOF), respectively. We expected that epigenetically driven developmental pathways regulated by CHD7 and KMT2D would overlap and that DNA methylation (DNAm) alterations downstream of the mutations in these genes would identify common target genes, elucidating a mechanistic link between these conditions, as well as specific target genes for each. more...

Organism:

Homo sapiens

Type:

Methylation profiling by genome tiling array

Platform:

GPL13534

235 Samples

Download data: IDAT

(Submitter supplied) Kabuki syndrome is a monogenic disorder caused by loss of function variants in either of two genes encoding histone-modifying enzymes. We performed targeted sequencing in a cohort of 27 probands with a clinical diagnosis of Kabuki syndrome. Of these, 12 had causative variants in the two known Kabuki syndrome genes. In 2, we identified presumptive loss of function de novo variants in KMT2A (missense and splice site variants), a gene that encodes another histone modifying enzyme previously exclusively associated with Wiedermann-Steiner syndrome. more...

Organism:

Homo sapiens

Type:

Methylation profiling by genome tiling array

Platform:

GPL13534

44 Samples

Download data: IDAT, TXT

(Submitter supplied) We compared the DNA methylation patterns in blood from individuals with two rare neurodevelopmental disorders (Childhood-onset dystonia (DYT-KMT2B) and Kabuki syndrome) and healthy control samples

Organism:

Homo sapiens

Type:

Methylation profiling by high throughput sequencing

Platform:

GPL20301

49 Samples

Download data: COV, TSV

(Submitter supplied) Disease-specific DNA methylation patterns (DNAm signatures) have been established for an increasing number of genetic disorders and represent a valuable tool for classification of genetic variants of uncertain significance (VUS). Sample size and batch effects are critical issues for establishing DNAm signatures, but their impact on the sensitivity and specificity of an already established DNAm signature as a predictive tool of variant pathogenicity has not previously been tested. more...

Organism:

Homo sapiens

Type:

Methylation profiling by genome tiling array

Platform:

GPL21145

62 Samples

Download data: IDAT, TXT

(Submitter supplied) We performed genome-wide transcriptome profiling in stable Kmt2d-/- (bi-allelic deletion of the catalytic SET domain) and Kmt2d+/+ ATDC5 chondrocyte cell lines 7 days after induction of differentiation and in stable Kmt2d-/- and Kmt2d+/+ undifferentiated ATDC5 cells.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

20 Samples

Download data: CSV, RDA

(Submitter supplied) Background Kabuki syndrome (KS) is a genetic disorder caused by DNA mutations in KMT2D, a lysine methyltransferase that methylates histones and other proteins, and therefore modifies chromatin structure and subsequent gene expression. Ketones, derived from the ketogenic diet, are histone deacetylase inhibitors that can ‘open’ chromatin and encourage gene expression. Preclinical studies have shown that the ketogenic diet rescues hippocampal memory neurogenesis in mice with KS via the epigenetic effects of ketones. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20301

5 Samples

Download data: MTX, TSV

(Submitter supplied) To evaluate the hypothesis that dysregulated thymocyte development contributes to immune deficiencies in individuals with KS1. We generated bulk murine CD4+ or CD8+ single positive thymocyte RNA-seq data from cells which lack the histone methyltransferase, Kmt2d SET domain (exons 50/51), with a conditional Cre-recombinase driven by Lck-CreMar (T cell specific) or Vav1-iCre (hematopoietic). Expression profiling by high throughput sequencing.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Third-party reanalysis

Platform:

GPL24247

18 Samples

Download data: BIGWIG, TSV, TXT

(Submitter supplied) Germline mutations in fundamental epigenetic regulatory molecules including DNA methyltransferase 3A (DNMT3A) are commonly associated with growth disorders, whereas somatic mutations are often associated with malignancy. We profiled genome-wide DNA methylation patterns in DNMT3A c.2312G>A; p.(Arg771Gln) carriers in a large Amish sibship with Tatton-Brown-Rahman syndrome (TBRS) and their mosaic father. more...

Organism:

Homo sapiens

Type:

Methylation profiling by genome tiling array

Platform:

GPL13534

12 Samples

Download data: IDAT, TXT

(Submitter supplied) Autism spectrum disorder (ASD) is a common and etiologically heterogeneous neurodevelopmental disorder. Although many genetic causes have been identified (>200 ASD-risk genes), no single gene mutation accounts for >1% of all ASD cases. A role for epigenetic mechanisms in ASD etiology is supported by the fact that many ASD-risk genes function as epigenetic regulators and evidence that epigenetic dysregulation can interrupt normal brain development. more...

Organism:

Homo sapiens

Type:

Methylation profiling by genome tiling array

Platform:

GPL13534

134 Samples

Download data: IDAT

(Submitter supplied) Growth deficiency is a characteristic feature of both Kabuki syndrome 1 (KS1) and Kabuki syndrome 2 (KS2), Mendelian disorders of the epigenetic machinery with similar phenotypes but distinct genetic etiologies. We previously described skeletal growth deficiency in a mouse model of KS1 and further established that a Kmt2d -/- chondrocyte model of KS1 exhibits precocious differentiation. Here we characterized growth deficiency in a mouse model of KS2, Kdm6a tm1d/+. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

32 Samples

Download data: SF

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL21103

63 Samples

Download data

(Submitter supplied) The Mendelian Disorders of the Epigenetic Machinery (MDEMs) have emerged as a class of Mendelian disorders caused by loss-of-function variants in epigenetic regulators. Although each MDEM has a different causative gene, they exhibit several overlapping disease manifestations. Here, we hypothesize that this phenotypic convergence is a consequence of common abnormalities at the epigenomic level, which directly or indirectly lead to downstream convergence at the transcriptomic level. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21103

27 Samples

Download data: CSV

(Submitter supplied) The Mendelian Disorders of the Epigenetic Machinery (MDEMs) have emerged as a class of Mendelian disorders caused by loss-of-function variants in epigenetic regulators. Although each MDEM has a different causative gene, they exhibit several overlapping disease manifestations. Here, we hypothesize that this phenotypic convergence is a consequence of common abnormalities at the epigenomic level, which directly or indirectly lead to downstream convergence at the transcriptomic level. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL21103

36 Samples

Download data: CSV

(Submitter supplied) We report RNA-seq from mouse E14.25 WT and KMT2D neural crest cell knockout palatal shelves

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL19057

6 Samples

Download data: TXT

(Submitter supplied) CHD7 is a member of the chromodomain helicase DNA binding domain family of ATP-dependent chromatin remodeling enzymes. De novo mutation of the CHD7 gene is a major cause of CHARGE syndrome, a genetic disease characterized by a complex constellation of birth defects. To gain insight to the function of CHD7, we mapped the distribution of the CHD7 protein on chromatin using the approach of chromatin immunoprecipitation on tiled microarrays (ChIP-chip). more...

Organism:

Homo sapiens; Mus musculus

Type:

Genome binding/occupancy profiling by genome tiling array

4 related Platforms

27 Samples

Download data: PAIR, TXT

(Submitter supplied) Regulation of chromatin plays fundamental roles in the normal development of the brain. Haploinsufficiency of the chromatin remodeling enzyme CHD7 causes CHARGE syndrome, a genetic disorder that prominently affects the development of the cerebellum. However, how CHD7 controls chromatin states in the cerebellum remains incompletely understood. Using conditional knockout of CHD7 in granule cell precursors in the mouse cerebellum, we find that CHD7 robustly promotes the accessibility and activity of enhancers in granule cell precursors. more...

Organism:

Homo sapiens; Mus musculus

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing; Other

Platforms:

GPL17021 GPL16791 GPL19057

104 Samples

Download data: BED, TXT, XLSX

(Submitter supplied) The genetic elements required to tune gene expression are partitioned in active and repressive nuclear condensates. These chromatin compartments include enhancer-associated clusters whose dynamic establishment and functioning depends on multivalent interactions occurring among transcription factors, cofactors and basal transcriptional machinery. However how chromatin modifiers contribute to the assembly of enhancer-associated condensates have not been addressed. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

12 Samples

Download data: BW, TXT

(Submitter supplied) Nicolaides-Baraitser syndrome (NCBRS) is a neurodevelopmental disorder caused by pathogenic sequence variants in SMARCA2 which encodes the catalytic component of the chromatin remodeling BAF (SWI/SNF) complex. We identified an NCBRS-SMARCA2 DNA methylation (DNAm) signature of 429 differentially methylated CpG sites in blood cells of individuals with NCBRS (n=8) compared to neurotypical controls (n=23) using the Illumina MethylationEPIC array. more...

Organism:

Homo sapiens

Type:

Methylation profiling by array

Platform:

GPL21145

44 Samples

Download data: IDAT, TXT

(Submitter supplied) We performed gene expression profiling analysis using data obtained from RNA-seq of 3 different cells types.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL30882

6 Samples

Download data: TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by array; Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL16791 GPL24432 GPL10558

185 Samples

Download data: BW, IDAT