Bilo, Larissa, Ochoa, Eguzkine, Lee, Sunwoo, Dey, Daniela, Kurth, Ingo, Kraft, Florian, Rodger, Fay, Docquier, France, Toribio, Ana, Bottolo, Leonardo, Binder, Gerhard, Fekete, György, Elbracht, Miriam, Maher, Eamonn R., Begemann, Matthias and Eggermann, Thomas (2023). Molecular characterisation of 36 multilocus imprinting disturbance (MLID) patients: a comprehensive approach. Clinical epigenetics, 15 (1),
Abstract
BACKGROUND: Imprinting disorders (ImpDis) comprise diseases which are caused by aberrant regulation of monoallelically and parent-of-origin-dependent expressed genes. A characteristic molecular change in ImpDis patients is aberrant methylation signatures at disease-specific loci, without an obvious DNA change at the specific differentially methylated region (DMR). However, there is a growing number of reports on multilocus imprinting disturbances (MLIDs), i.e. aberrant methylation at different DMRs in the same patient. These MLIDs account for a significant number of patients with specific ImpDis, and several reports indicate a central role of pathogenic maternal effect variants in their aetiology by affecting the maturation of the oocyte and the early embryo. Though several studies on the prevalence and the molecular causes of MLID have been conducted, homogeneous datasets comprising both genomic and methylation data are still lacking. RESULTS: Based on a cohort of 36 MLID patients, we here present both methylation data obtained from next-generation sequencing (NGS, ImprintSeq) approaches and whole-exome sequencing (WES). The compilation of methylation data did not reveal a disease-specific MLID episignature, and a predisposition for the phenotypic modification was not obvious as well. In fact, this lack of epigenotype-phenotype correlation might be related to the mosaic distribution of imprinting defects and their functional relevance in specific tissues. CONCLUSIONS: Due to the higher sensitivity of NGS-based approaches, we suggest that ImprintSeq might be offered at reference centres in case of ImpDis patients with unusual phenotypes but MLID negative by conventional tests. By WES, additional MLID causes than the already known maternal effect variants could not be identified, neither in the patients nor in the maternal exomes. In cases with negative WES results, it is currently unclear to what extent either environmental factors or undetected genetic variants contribute to MLID.
Publication DOI: | https://doi.org/10.1186/s13148-023-01453-5 |
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Divisions: | College of Health & Life Sciences > Aston Medical School |
Funding Information: | Open Access funding enabled and organized by Projekt DEAL. The study is funded by the Deutsche Forschungsgemeinschaft (DFG, EG113/15–1) and supported by the Genomics Facility, a core facility of the Interdisciplinary Center for Clinical Research (IZKF) Aa |
Additional Information: | Copyright © The Author(s), 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (https://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
Uncontrolled Keywords: | DNA Methylation,Genomics,Genotype,High-Throughput Nucleotide Sequencing |
Publication ISSN: | 1868-7083 |
Last Modified: | 06 Aug 2024 09:58 |
Date Deposited: | 03 Jan 2024 18:42 |
Full Text Link: | |
Related URLs: |
https://clinica ... 148-023-01453-5
(Publisher URL) http://www.scop ... tnerID=8YFLogxK (Scopus URL) |
PURE Output Type: | Article |
Published Date: | 2023-03-01 |
Accepted Date: | 2023-02-20 |
Authors: |
Bilo, Larissa
Ochoa, Eguzkine Lee, Sunwoo Dey, Daniela Kurth, Ingo Kraft, Florian Rodger, Fay Docquier, France Toribio, Ana Bottolo, Leonardo Binder, Gerhard Fekete, György Elbracht, Miriam Maher, Eamonn R. Begemann, Matthias Eggermann, Thomas |