GEO DataSets

(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) 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) 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) 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) 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) 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) 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) 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) Coffin-Siris and Nicolaides-Baraitser syndromes (CSS and NCBRS) are Mendelian disorders caused by mutations in subunits of the BAF chromatin remodeling complex. We report overlapping peripheral blood DNA methylation epi-signatures in individuals with various subtypes of CSS (ARID1B, SMARCB1, and SMARCA4) and NCBRS (SMARCA2). We demonstrate that the degree of similarity in the epi-signatures of some CSS subtypes and NCBRS can be greater than that within CSS, indicating a link in the functional basis of the two syndromes. more...

Organism:

Homo sapiens

Type:

Methylation profiling by genome tiling array

Platforms:

GPL13534 GPL21145

29 Samples

Download data: IDAT, TXT

(Submitter supplied) Kabuki syndrome is a Mendelian intellectual disability syndrome caused by mutations in either of two genes (KMT2D and KDM6A) involved in chromatin accessibility. We previously showed that an agent that promotes chromatin opening, the histone deacetylase inhibitor (HDACi) AR-42, ameliorates the deficiency of adult neurogenesis in the granule cell layer of the dentate gyrus, and rescues hippocampal memory defects in a mouse model of Kabuki syndrome (Kmt2d+/βGeo). more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL6246

13 Samples

Download data: CEL

(Submitter supplied) Sequence-based genetic testing identifies causative variants in ~50% of individuals with developmental and epileptic encephalopathies (DEEs). Aberrant changes in DNA methylation are implicated in various neurodevelopmental disorders but remain unstudied in DEEs. We interrogate the diagnostic utility of genome-wide DNA methylation array analysis on peripheral blood samples from 582 individuals with genetically unsolved DEEs. more...

Organism:

Homo sapiens

Type:

Methylation profiling by array

Platform:

GPL21145

290 Samples

Download data: IDAT, TXT

(Submitter supplied) Objective: Cocaine use disorders (CUD) represent a major public health problem in many countries. To better understand the interaction between the environmental modulations and phenotype, the aim of the present study was to investigate the DNA methylation pattern of CUD patients, which were concomitant dependents of cocaine and crack, and healthy controls. Methods: We studied DNA methylation profiles in the peripheral blood of 23 CUD patients and 24 healthy control subjects using the Illumina Infinium HumanMethylation450 BeadChip arrays. more...

Organism:

Homo sapiens

Type:

Methylation profiling by genome tiling array

Platform:

GPL13534

47 Samples

Download data: IDAT