Comparison of Methylation Episignatures in KMT2B and KMT2D-related human disorders

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 Overall design: Aim&Methods: To investigate peripheral blood methylation episignatures in KMT2B-related dystonia (DYT-KMT2B), we undertook genome-wide methylation profiling of ~2M CpGs using a next-generation sequencing based assay and compared the findings to those in controls and patients with Kabuki syndrome Type 1 (KS1-KMT2D). Results: 1,812 significantly differentially methylated CpG positions (DMPs) (FDR < 0.05) were detected in DYT-KMT2B samples compared to controls. Multi-dimensional scaling analysis showed that the 10 DYT-KMT2B samples clustered together and separately from 29 controls and 10 with pathogenic variants in KMT2D. We found that most DMPs were specific to one disorder and that all (DYT-KMT2B) and most (KS1) methylation alterations in CpG islands were gain of methylation events Processed data include 1) bismark CpG coverage file for all 20 samples and 29 healthy controls and 2) significant differentially methylated DMPs for each cohort group (DYT-KMT2B vs Control, KS1 vs Control, DYT-KMT2B and KS1 (without KMT2D_5) vs Control, and KS1 (without KMT2D_5 vs Control). Final betavalues, CpG site information and NGS-ID (generated by RnBeads package) per sample are provided in each file. In detail, we found 1,812 significantly differentially methylated CpG positions in DYT-KMT2B cohort, 89 DMPs in KS1 cohort, 677 DMPs in DYT-KMT2B+KS1 (without KMT2D_5) cohort, and 136 DMPs in KS1 (without KMT2D_5) cohort.