Shaping the epigenetic basis of Werner Syndrome

AUTORI

ABSTRACT

Werner syndrome is an autosomal recessive genetic disease responsible for a progeroid disorder including a plethora of premature clinical signs traditionally associated with physiological ageing. The molecular alterations that lead to all phenotypes associated the disease remain still unidentified. Here we describe our recent findings and results from literature about the possibility that epigenetic changes could be associated with Werner syndrome phenotype. Recent literature evidences that epigenetic mechanisms are at the basis of both physiological and pathological processes, like insulin production and secretion. Analysis of genome-wide DNA methylation profile in the whole blood from patients affected by Werner syndrome demonstrated enrichment of hypermethylated probes in glycosphingolipid biosynthesis, FoxO signalling and insulin signalling pathways, while hypomethylated probes were enriched in PI3KAkt signalling and focal adhesion pathways. Twenty-two differentially methylated genes belonging to the enriched pathways resulted differentially expressed in Werner syndrome fibroblasts. DNA methylation profiles analysis in Werner syndrome patients revealed differentially methylated regions in genes involved in other ageing phenotypes or associated syndromes like systemic sclerosis, dyskeratosis congenita and Down syndrome. Genome-wide epigenetics changes observed in the peripheral blood from patients with Werner syndrome provide new insight in the pathogenesis of the disease, highlighting in some cases a functional correlation of gene expression and methylation status

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