Fig. 1. Peripheral blood cells of DOS patients with DNMT3A^R882 mutations have a more severe methylation phenotype than non-R882 mutations.

a Distribution of germline DNMT3A mutations identified in DOS patients from this study. b Density plot of methylation values from whole-genome bisulfite sequencing (WGBS) for CpGs within DMRs for each peripheral blood sample from healthy donors (red; n = 15), DNMT3A^R882 (blue, n = 3), and DNMT3A^non-R882 (green, n = 8) patients. c Mean methylation values for both global CpGs and DMR-associated CpGs in specific, annotated regions of the genome. Hypothesis testing was performed via two-way repeated-measures ANOVA with Tukey’s multiple comparison test within each genomic region. (ns = not significant, **p ≦ 0.01, ****p ≦ 0.001). d Mean Size (in bp) of DMRs identified in DNMT3A^R882 (n = 2,209) and DNMT3A^non-R882 (n = 332) peripheral blood samples (P = 0.0587, two-tailed t test). e Heatmap showing the mean methylation values for the 2209 DMRs defined in b for each individual healthy donor and DNMT3A^R882 sample. The values for the same DMRs were also plotted passively for DNMT3A^non-R882 samples (age and sex shown below). f Heatmap showing the mean CpG methylation values for the 332 DMRs defined by comparing the healthy donors and DNMT3A^non-R882 samples. Values for the same DMRs were plotted passively for DNMT3A^R882 samples (age and sex shown below). g Examples of DMRs within the HOXB cluster and RASIP1 gene. Healthy donors are shown in red, DNMT3A^R882 cases in blue, and DNMT3A^non-R882 cases in green. Gene tracks are shown below, and DMRs are designated in boxes. DMR differentially methylated region, bp base pairs, TSS transcriptional start site.