Comparison of methylation episignatures in KMT2B- and KMT2D-related human disorders
| Autor: | Sunwoo Lee, Eguzkine Ochoa, Katy Barwick, Laura Cif, Fay Rodger, France Docquier, Belén Pérez-Dueñas, Graeme Clark, Ezequiel Martin, Siddharth Banka, Manju A Kurian, Eamonn R Maher |
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| Přispěvatelé: | Lee, Sunwoo [0000-0003-2806-3268], Pérez-Dueñas, Belén [0000-0002-4979-2788], Banka, Siddharth [0000-0002-8527-2210], Kurian, Manju A [0000-0003-3529-5075], Maher, Eamonn R [0000-0002-6226-6918], Apollo - University of Cambridge Repository, Maher, Eamonn [0000-0002-6226-6918] |
| Rok vydání: | 2022 |
| Předmět: |
Cancer Research
Hematologic Diseases/blood Histone-Lysine N-Methyltransferase/genetics Neoplasm Proteins/genetics Genetics Humans Abnormalities Multiple Kabuki syndrome early-onset dystonia Histone-Lysine N-Methyltransferase Face/abnormalities Vestibular Diseases/blood DNA Methylation neurodevelopmental disorder Hematologic Diseases Neoplasm Proteins DNA-Binding Proteins histone lysine methyltransferases (KMTs) Phenotype Vestibular Diseases Face Mutation methylation DNA-Binding Proteins/genetics Research Article chromatin disorders |
| Zdroj: | Lee, S, Ochoa, E, Barwick, K, Cif, L, Rodger, F, Docquier, F, Pérez-Dueñas, B, Clark, G, Martin, E, Banka, S, Kurian, M A & Maher, E R 2022, ' Comparison of methylation episignatures in KMT2B-and KMT2D-related human disorders ', Epigenomics, vol. 14, no. 9, pp. 537-547 . https://doi.org/10.2217/epi-2021-0521 |
| ISSN: | 1750-192X 1750-1911 |
| Popis: | Funder: Rosetrees Trust 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. |
| Databáze: | OpenAIRE |
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