Disturbed Methylation at Multiple Imprinted Loci: an Increasing Observation in Imprinting Disorders

Abstract

The widely accepted association between aberrant methylation at specific imprinted loci and distinct imprinting disorders has recently been brought into question by the identification of methylation defects at multiple loci (multilocus methylation defect [MLMD]). Strikingly, in different imprinting disorders, the same MLMD patterns can be observed. The cause for this ambiguous epigenotype–phenotype correlation is currently unknown. Future strategies to solve this enigma have to include all levels of imprinting regulation, ranging from DNA methylation to chromatin organization, as any disturbance of the balanced interaction between the different players in imprinting regulation might cause disturbed expression of imprinted factors. The molecular analysis of MLMD will help in discovering these interactions and contribute to the understanding of genomic imprinting and its disturbances.

KEYWORDS::

• epigenotype
• epimutation
• imprinting disorder
• methylation defect
• multilocus

Financial & competing interests disclosure

The authors are supported by the Bundesministerium für Bildung und Forschung (Network ‘Imprinting Diseases‘, 01GM0884), MerckSerono and the Else Kröner Fresenius-Stiftung. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

The authors are supported by the Bundesministerium für Bildung und Forschung (Network ‘Imprinting Diseases‘, 01GM0884), MerckSerono and the Else Kröner Fresenius-Stiftung. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.