Imprinting disorders: a group of congenital disorders with overlapping patterns of molecular changes affecting imprinted loci

Abstract

Congenital imprinting disorders (IDs) are characterised by molecular changes affecting imprinted chromosomal regions and genes, i.e. genes that are expressed in a parent-of-origin specific manner. Recent years have seen a great expansion in the range of alterations in regulation, dosage or DNA sequence shown to disturb imprinted gene expression, and the correspondingly broad range of resultant clinical syndromes. At the same time, however, it has become clear that this diversity of IDs has common underlying principles, not only in shared molecular mechanisms, but also in interrelated clinical impacts upon growth, development and metabolism. Thus, detailed and systematic analysis of IDs can not only identify unifying principles of molecular epigenetics in health and disease, but also support personalisation of diagnosis and management for individual patients and families.

Asymmetric DNA methylation of CpG dyads is a feature of secondary DMRs associated with the Dlk1/Gtl2 imprinting cluster in mouse

“…Stably maintaining DNA methylation at imprinted loci is critical for normal growth and development, and aberrant DNA methylation patterns are associated not only with abnormal expression of imprinted genes, but also with multiple imprinting disorders [38, 39]. Therefore, understanding the normal methylation patterns and how they are altered are important for elucidating the regulation of imprinted genes.…”

Epigenetics and obesity cardiomyopathy: From pathophysiology to prevention and management

“…Each imprinting disorder is characterized by unique clinical features associated with specific imprinting defects for development, growth and metabolism. The diverse imprinting disorders share common features, not only in molecular mechanisms, but also in outcomes of development, growth and metabolism (Eggermann et al, 2015a;Eggermann et al, 2015b). Not surprisingly, a systematic analysis of imprinting disorders should help not only to reveal mechanisms behind epigenetic changes in health and disease, but also to guide personalization of diagnosis and treatment from the perspective of precision medicine.…”

Hypercortisolism due to a Pituitary Adenoma Associated with Beckwith-Wiedemann Syndrome

“…Phenotypic presentation of BWS is extremely variable, with some patients presenting with a complete phenotype, and some patients showing only minor symptoms of the disease [14]. This can be explained by the underlying molecular defect [1,3,4] and/or the rate of mosaicism, with patients with a high level of affected cells presenting with a more severe phenotype.…”