Epigenetics Relating to Wilson Disease

Abstract It is well established that copper accumulation in patients with Wilson disease (WD) is due to mutations affecting the ATP7B copper transporter gene. However, the variable clinical presentation suggests that other factors, including epigenetic mechanisms, contribute to the disease phenotype. Epigenetics refers to the study of changes in gene expression due to noncoding RNAs and reversible modifications of chromosomes, including DNA methylation and histone modifications. DNA methylation requires an adequate supply of methyl donors such as methionine. Underlying changes in methionine metabolism can affect DNA methylation and ultimately disease progression. Additionally, environmental effects such as diet, lifestyle, and toxin exposure, both in utero and postnatally, are known to impact gene expression through epigenetic mechanisms. Evidence in animal models of WD and indirect clinical evidence indicates changes in methionine metabolism, and consequently epigenetic mechanisms may contribute to disease presentation and course.