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

Abstract

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.

Publication DOI: https://doi.org/10.2217/epi-2021-0521
Divisions: College of Health & Life Sciences > Aston Medical School
Funding Information: This research was co-funded by the NIHR Cambridge Biomedical Research Centre and Rosetrees Trust (to E Ochoa, S Lee and ER Maher). The University of Cambridge has received salary support (ER Maher) from the NHS in the East of England through the Clinical
Additional Information: Copyright © 2022, The Authors. This work is licensed under the Creative Commons Attribution 4.0 License. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/
Uncontrolled Keywords: Chromatin disorders,early-onset dystonia,histone lysine methyltransferases (KMTs),Kabuki syndrom,methylation,neurodevelopmental disorder
Publication ISSN: 1750-192X
Last Modified: 09 Dec 2024 09:08
Date Deposited: 04 Jan 2024 15:47
Full Text Link:
Related URLs: https://www.fut ... 7/epi-2021-0521 (Publisher URL)
PURE Output Type: Article
Published Date: 2022-05-04
Published Online Date: 2022-05-04
Accepted Date: 2022-04-04
Authors: Lee, Sunwoo
Ochoa, Eguzkine
Barwick, Katy
Cif, Laura
Rodger, Fay
Docquier, France
Pérez-Dueñas, Bélen
Clark, Graeme
Martin, Ezequiel
Banka, Siddharth
Kurian, Manju A.
Maher, Eamonn R.

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