Comparison of methylation episignatures in KMT2B- and KMT2D-related human disorders

Sunwoo Lee, Eguzkine Ochoa, Katy Barwick, Laura Cif, Fay Rodger, France Docquier, Bélen Pérez-Dueñas, Graeme Clark, Ezequiel Martin, Siddharth Banka, Manju A. Kurian, Eamonn R. Maher

Research output: Contribution to journalArticlepeer-review


Aim & methods: To investigate peripheral blood methylation episignatures in KMT2B-related dystonia (DYT-KMT2B), the authors undertook genome-wide methylation profiling of ∼2 M CpGs using a next-generation sequencing-based assay and compared the findings with those in controls and patients with KMT2D-related Kabuki syndrome type 1 (KS1). Results: A total of 1812 significantly differentially methylated CpG positions (false discovery rate < 0.05) were detected in DYT-KMT2B samples compared with 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. The authors found that most differentially methylated CpG positions were specific to one disorder and that all (DYT-KMT2B) and most (Kabuki syndrome type 1) methylation alterations in CpG islands were gain of methylation events. Conclusion: Using sensitive methylation profiling methodology, the authors replicated recent reports of a methylation episignature for DYT-KMT2B. These findings will facilitate the development of episignature-based assays to improve diagnostic accuracy.

Original languageEnglish
Pages (from-to)537-547
Number of pages11
Issue number9
Early online date4 May 2022
Publication statusPublished - 4 May 2022

Bibliographical note

Copyright © 2022, The Authors. This work is licensed under the Creative Commons Attribution 4.0 License. To view a copy of this license, visit


  • Chromatin disorders
  • early-onset dystonia
  • histone lysine methyltransferases (KMTs)
  • Kabuki syndrom
  • methylation
  • neurodevelopmental disorder


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