Garau, Jessica, Charras, Amandine, Varesio, Costanza, Orcesi, Simona, Dragoni, Francesca, Galli, Jessica, Fazzi, Elisa, Gagliardi, Stella, Pansarasa, Orietta, Cereda, Cristina et al (show 1 more authors)
(2023)
Altered DNA methylation and gene expression predict disease severity in patients with Aicardi-Goutieres syndrome.
CLINICAL IMMUNOLOGY, 249.
109299-.
|
PDF
Garau CLIM 2023.pdf - Open Access published version Download (6MB) | Preview |
Abstract
Aicardi-Goutières Syndrome (AGS) is a rare neuro-inflammatory disease characterized by increased expression of interferon-stimulated genes (ISGs). Disease-causing mutations are present in genes associated with innate antiviral responses. Disease presentation and severity vary, even between patients with identical mutations from the same family. This study investigated DNA methylation signatures in PBMCs to understand phenotypic heterogeneity in AGS patients with mutations in RNASEH2B. AGS patients presented hypomethylation of ISGs and differential methylation patterns (DMPs) in genes involved in "neutrophil and platelet activation". Patients with "mild" phenotypes exhibited DMPs in genes involved in "DNA damage and repair", whereas patients with "severe" phenotypes had DMPs in "cell fate commitment" and "organ development" associated genes. DMPs in two ISGs (IFI44L, RSAD2) associated with increased gene expression in patients with "severe" when compared to "mild" phenotypes. In conclusion, altered DNA methylation and ISG expression as biomarkers and potential future treatment targets in AGS.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Aicardi-Goutie `res syndrome, DNA methylation, RNASEH2B, Phenotype, Biomarker, Interferon, ISG |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 17 Apr 2023 07:46 |
| Last Modified: | 05 May 2023 14:01 |
| DOI: | 10.1016/j.clim.2023.109299 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3169585 |
Dimensions
Dimensions
