Mackay, Deborah J. G., Gazdagh, Gabriella, Monk, David, Brioude, Frederic, Giabicani, Eloise, Krzyzewska, Izabela M., Kalish, Jennifer M., Maas, Saskia M., Kagami, Masayo, Beygo, Jasmin, Kahre, Tiina, Tenorio-Castano, Jair, Ambrozaitytė, Laima, Burnytė, Birutė, Cerrato, Flavia, Davies, Justin H., Ferrero, Giovanni Battista, Fjodorova, Olga, Manero-Azua, Africa, Pereda, Arrate, Russo, Silvia, Tannorella, Pierpaola, Temple, Karen I., Õunap, Katrin, Riccio, Andrea, de Nanclares, Guiomar Perez, Maher, Eamonn R., Lapunzina, Pablo, Netchine, Irène, Eggermann, Thomas, Bliek, Jet and Tümer, Zeynep (2024). Multi-locus imprinting disturbance (MLID): interim joint statement for clinical and molecular diagnosis. Clinical epigenetics, 16 (1),
Abstract
Background: Imprinting disorders are rare diseases resulting from altered expression of imprinted genes, which exhibit parent-of-origin-specific expression patterns regulated through differential DNA methylation. A subgroup of patients with imprinting disorders have DNA methylation changes at multiple imprinted loci, a condition referred to as multi-locus imprinting disturbance (MLID). MLID is recognised in most but not all imprinting disorders and is also found in individuals with atypical clinical features; the presence of MLID often alters the management or prognosis of the affected person. Some cases of MLID are caused by trans-acting genetic variants, frequently not in the patients but their mothers, which have counselling implications. There is currently no consensus on the definition of MLID, clinical indications prompting testing, molecular procedures and methods for epigenetic and genetic diagnosis, recommendations for laboratory reporting, considerations for counselling, and implications for prognosis and management. The purpose of this study is thus to cover this unmet need. Methods: A comprehensive literature search was conducted resulting in identification of more than 100 articles which formed the basis of discussions by two working groups focusing on clinical diagnosis (n = 12 members) and molecular testing (n = 19 members). Following eight months of preparations and regular online discussions, the experts from 11 countries compiled the preliminary documentation and determined the questions to be addressed during a face-to-face meeting which was held with the attendance of the experts together with four representatives of patient advocacy organisations. Results: In light of available evidence and expert consensus, we formulated 16 propositions and 8 recommendations as interim guidance for the clinical and molecular diagnosis of MLID. Conclusions: MLID is a molecular designation, and for patients with MLID and atypical phenotypes, we propose the alternative term multi-locus imprinting syndrome. Due to the intrinsic variability of MLID, the guidelines underscore the importance of involving experts from various fields to ensure a confident approach to diagnosis, counselling, and care. The authors advocate for global, collaborative efforts in both basic and translational research to tackle numerous crucial questions that currently lack answers, and suggest reconvening within the next 3–5 years to evaluate the research advancements and update this guidance as needed.
Publication DOI: | https://doi.org/10.1186/s13148-024-01713-y |
---|---|
Divisions: | College of Health & Life Sciences > Aston Medical School |
Funding Information: | This study is supported by EJP RD Networking Support Scheme round 10 (40-46300-98-1094). KO and TK are supported by Estonian Research Council Grants PRG471 and PRG2040. |
Additional Information: | Copyright © The Author(s) 2024. 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: | MLID,Molecular diagnosis,Imprinting disorder,Multi-locus imprinting disturbance,Differentially methylated regions,DMR,Clinical diagnosis |
Publication ISSN: | 1868-7083 |
Data Access Statement: | No datasets were generated or analysed during the current study. |
Last Modified: | 12 Aug 2024 11:33 |
Date Deposited: | 05 Aug 2024 12:27 |
Full Text Link: | |
Related URLs: |
https://clinica ... 148-024-01713-y
(Publisher URL) |
PURE Output Type: | Review article |
Published Date: | 2024-12 |
Published Online Date: | 2024-08-01 |
Accepted Date: | 2024-07-24 |
Authors: |
Mackay, Deborah J. G.
Gazdagh, Gabriella Monk, David Brioude, Frederic Giabicani, Eloise Krzyzewska, Izabela M. Kalish, Jennifer M. Maas, Saskia M. Kagami, Masayo Beygo, Jasmin Kahre, Tiina Tenorio-Castano, Jair Ambrozaitytė, Laima Burnytė, Birutė Cerrato, Flavia Davies, Justin H. Ferrero, Giovanni Battista Fjodorova, Olga Manero-Azua, Africa Pereda, Arrate Russo, Silvia Tannorella, Pierpaola Temple, Karen I. Õunap, Katrin Riccio, Andrea de Nanclares, Guiomar Perez Maher, Eamonn R. Lapunzina, Pablo Netchine, Irène Eggermann, Thomas Bliek, Jet Tümer, Zeynep |