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