DNA methylation signatures in Blood DNA of Hutchinson–Gilford Progeria syndrome

• DOI: 10.1111/acel.13555
• Publication Date: 2022-01-19T19:10:26Z
• Authors: Yosra Bejaoui; Aleem Razzaq; Noha A. Yousri; Junko Oshima; Andre Megarbane; Abeer Qannan; Ramya Potabattula; Tanvir Alam; George M. Martin; Henning F. Horn; Thomas Haaf; Steve Horvath; Nady El Hajj
• Keywords: Progeria; CpG site; LMNA; Premature aging; Werner syndrome

Hutchinson-Gilford Progeria Syndrome (HGPS) is an extremely rare genetic disorder caused by mutations in the LMNA gene and characterized premature accelerated aging beginning childhood. In this study, we performed first genome-wide methylation analysis on blood DNA of 15 patients with progeroid laminopathies using Infinium Methylation EPIC arrays including 8 classical HGPS. We could observe alterations at 61 CpG sites as well 32 significant regions following a 5 Kb tiling analysis. Differentially methylated probes were enriched for phosphatidylinositol biosynthetic process, phospholipid sarcoplasm, sarcoplasmic reticulum, phosphatase regulator activity, glycerolipid glycerophospholipid metabolic process. Differential level promoters islands revealed no changes laminopathy patients. Nevertheless, differences classic HGPS when specifically looking overlapping solo-WCGW partially domains. Comparing aberrantly laminopathies, Werner syndrome, Down syndrome common significantly hypermethylated region close vicinity to transcription start site long non-coding RNA located anti-sense Catenin Beta Interacting Protein 1 (CTNNBIP1). By characterizing epigenetically altered sites, identify possible pathways/mechanisms that might have role laminopathies.