Hypomethylation of the MEG8:Int2-DMR in patients with pathogenic PLAG1 variants suggests new role of the chr14q32 imprinting cluster in Silver-Russell syndrome
Our results indicate that pathogenic PLAG1 variants leading to stable aberrant PLAG1 proteins and possibly acting in a dominant-negative manner influence methylation of the MEG8 locus. This study suggests a new pathogenetic mechanism of the PLAG1 gene in SRS, involving imprinted genes in the chr14q32 cluster through deregulation of the MEG8:Int2-DMR and provides an epigenetic signature that may be used to assess the damaging potential of the PLAG1 variants.
Authors
- Carlo Giaccari (ORCID: https://orcid.org/0000-0002-5476-5362)
- Maria Vittoria Cubellis (ORCID: https://orcid.org/0000-0001-6147-6553)
- Francesco Cecere (ORCID: https://orcid.org/0000-0002-0329-0870)
- Andrea Riccio (ORCID: https://orcid.org/0000-0001-7990-3576)
- José Ramón Fernández‐Fructuoso (ORCID: https://orcid.org/0000-0001-8488-4509)
- Laura Pignata (ORCID: https://orcid.org/0000-0001-8835-5567)
- Emilia D’Angelo (ORCID: https://orcid.org/0009-0001-1356-0395)
- Irène Netchine (ORCID: https://orcid.org/0000-0003-1324-3389)
- Nathalie Thibaud
- Silvia Russo (ORCID: https://orcid.org/0000-0002-5893-0193)
- Flavia Cerrato (ORCID: https://orcid.org/0000-0003-3794-3021)
- Alessandro Vimercati (ORCID: https://orcid.org/0000-0002-7918-584X)
- Frédéric Brioude (ORCID: https://orcid.org/0000-0001-8122-760X)
- Abu Saadat (ORCID: https://orcid.org/0000-0001-9636-2513)
- Thomas Eggermann
Institutions
- Inserm (FR)
- University of Tennessee Health Science Center (US)
- Sorbonne Université (FR)
- Hôpital Armand-Trousseau (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- University of Campania "Luigi Vanvitelli" (IT)
- IRCCS Istituto Auxologico Italiano (IT)
- Centre de Recherche Saint-Antoine (FR)
- Institute of Genetics and Biophysics (IT)
- University of Naples Federico II (IT)
- RWTH Aachen University (DE)
Publication Details
- Journal
- Clinical Epigenetics
- Published
- 2025-11-23
- DOI
- https://doi.org/10.1186/s13148-025-02024-6
- Primary Topic
- Genetic Syndromes and Imprinting
- Type
- article
- Field-Weighted Citation Impact
- 0.00