Journal: Genome Medicine

Article Title: Identification of an episignature for CHD3 -related Snijders Blok-Campeau syndrome reveals heterogeneity in the CHARGE syndrome episignature: towards a better characterisation of chromatinopathies

doi: 10.1186/s13073-026-01639-5

Figure Lengend Snippet: A Principal component analysis of adjusted methylation levels, after correcting for expected methylation based on age, sex, and estimated blood cell counts. Status is indicated by colour: green for controls, red for CHD3 typical, purple for CHD3 atypical, blue for CHD3 VUS, while phenotype is determined based on point size, with small points representing controls, mild phenotypes, and not available; medium-sized points representing moderate phenotypes; and large points representing severe phenotypes. The percentage of explained variance is provided for each axis. B Heatmap of adjusted methylation levels displays hierarchical clustering of controls and patients with CHD3 LP/P variants and CHD3 VUS. Blue indicates hypo-methylated positions while red indicates hyper-methylated positions with respect to expected methylation levels at equivalent age, sex and inferred blood cell composition. Status is indicated by colour: green for controls, red for CHD3 typical, purple for CHD3 atypical, and blue for CHD3 VUS. The technology used for each sample is also indicated: yellow for EPIC v1.0 and orange for EPIC v2.0. Also the origin is indicated: grey for Diagenode platform and brown for Rouen. C Pathogenicity scores for each patient with CHD3 LP/P variants were obtained by leave-one-out, and pathogenicity scores for CHD3 atypical and CHD3 VUS were derived from a prediction model based on the complete training set, using a support vector machine predictor. Colours follow the same rules as in panels A and B. D Barplot representing the Gene Ontology (GO) enrichment analysis of differentially methylated genes for DMRs of the CHD3 signature. The x-axis represents the number of genes associated with each Biological Process category. The colour gradient indicates the adjusted p-value, with lower p-values (higher significance) shown in pink and higher p-values in blue

Article Snippet: More recently, pathogenic variants in CHD1 (Pilarowski-Bjornsson syndrome; ORPHA:529965), CHD2 (developmental and epileptic encephalopathy 94; ORPHA:2382 and more precisely MIM #615369), CHD3 (Snijders Blok-Campeau syndrome; ORPHA:599082), CHD4 (Sifrim-Hitz-Weiss syndrome; ORPHA:653712), CHD5 (Parenti-Mignot neurodevelopmental syndrome; MIM #619873), and CHD6 (Hallermann-Streiff syndrome; ORPHA:2108) have also been reported in neurodevelopmental disorders [ – ].

Techniques: Methylation, Derivative Assay, Plasmid Preparation

Journal: Genome Medicine

Article Title: Identification of an episignature for CHD3 -related Snijders Blok-Campeau syndrome reveals heterogeneity in the CHARGE syndrome episignature: towards a better characterisation of chromatinopathies

doi: 10.1186/s13073-026-01639-5

Figure Lengend Snippet: A Breakdown histogram showing the number of clinical phenotypes associated with each disease based on data from the MONDO database ( https://monarchinitiative.org/ ). B Principal component analysis of adjusted methylation levels, after correcting for expected methylation based on age, sex, and inferred blood cell composition. The probes used correspond to the union of the CHD7 , CHD8 (previously published), and CHD3 (newly identified DMPs) signatures (Additional file 5). Status is indicated by colour: green for controls, red for CHD3 typical patients, purple for CHD8 patients, and orange for CHD7 patients, with a further separation into two subgroups among CHD7 patients, one of which is outlined in black. C Heatmap of adjusted methylation levels, displaying hierarchical clustering of controls and CHD3 typical, CHD8 , and CHD7 patients. Hypomethylated regions are shown in blue, while hypermethylated regions appear in red, relative to the expected methylation levels for individuals of the same age, sex, and inferred blood cell composition. Colours follow the same scheme as in the principal component analysis above. D Raincloud plot illustrating the distribution of adjusted methylation levels. For each category, a mean methylation level is computed per block and per individual, generating a density plot for each group. Below each density distribution, a boxplot visualises the spread of individual data points. Colours follow the same scheme as in the plots on the left. P-values were determined using the Wilcoxon test. Each patient category was compared to the controls, and the two CHD7 subgroups were also compared to each other

Article Snippet: More recently, pathogenic variants in CHD1 (Pilarowski-Bjornsson syndrome; ORPHA:529965), CHD2 (developmental and epileptic encephalopathy 94; ORPHA:2382 and more precisely MIM #615369), CHD3 (Snijders Blok-Campeau syndrome; ORPHA:599082), CHD4 (Sifrim-Hitz-Weiss syndrome; ORPHA:653712), CHD5 (Parenti-Mignot neurodevelopmental syndrome; MIM #619873), and CHD6 (Hallermann-Streiff syndrome; ORPHA:2108) have also been reported in neurodevelopmental disorders [ – ].

Techniques: Methylation, Blocking Assay

Journal: Genome Medicine

Article Title: Identification of an episignature for CHD3 -related Snijders Blok-Campeau syndrome reveals heterogeneity in the CHARGE syndrome episignature: towards a better characterisation of chromatinopathies

doi: 10.1186/s13073-026-01639-5

Figure Lengend Snippet: A , B , C , D , E IGV visualisation examples showing DMPs, DMRs, and CHD3 ChIP-Seq results (public data, see Mat & Meth), which often colocalise at gene promoters. F Venn diagram representing the common positions between DMPs and DMRs of the CHD3 signature and CHD3 ChIP-Seq

Article Snippet: More recently, pathogenic variants in CHD1 (Pilarowski-Bjornsson syndrome; ORPHA:529965), CHD2 (developmental and epileptic encephalopathy 94; ORPHA:2382 and more precisely MIM #615369), CHD3 (Snijders Blok-Campeau syndrome; ORPHA:599082), CHD4 (Sifrim-Hitz-Weiss syndrome; ORPHA:653712), CHD5 (Parenti-Mignot neurodevelopmental syndrome; MIM #619873), and CHD6 (Hallermann-Streiff syndrome; ORPHA:2108) have also been reported in neurodevelopmental disorders [ – ].

Techniques: ChIP-sequencing