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


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Authors
Ochoa, Eguzkine 
Barwick, Katy 
Cif, Laura 
Rodger, Fay 
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.

Description

Funder: Rosetrees Trust

Keywords
Research Article, chromatin disorders, early-onset dystonia, histone lysine methyltransferases (KMTs), Kabuki syndrome, methylation, neurodevelopmental disorder
Journal Title
Epigenomics
Conference Name
Journal ISSN
1750-1911
1750-192X
Volume Title
0
Publisher
Future Medicine Ltd
Sponsorship
NIHR (Cambridge Biomedical Research Centre)