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Review
. 2015 Nov 14:7:123.
doi: 10.1186/s13148-015-0143-8. eCollection 2015.

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

Thomas Eggermann  1 , Guiomar Perez de Nanclares  2 , Eamonn R Maher  3 , I Karen Temple  4 , Zeynep Tümer  5 , David Monk  6 , Deborah J G Mackay  4 , Karen Grønskov  5 , Andrea Riccio  7 , Agnès Linglart  8 , Irène Netchine  9
Affiliations
Review

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

Thomas Eggermann et al. Clin Epigenetics. .

Erratum in

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.

Keywords: Epimutation; Imprinted genes; Imprinting disorders; Uniparental disomy.

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Figures

Fig. 1
Fig. 1
PLAGL1 imprinted region on chromosome 6q24, altered in TNDM. The currently known imprinted loci associated with one of the known IDs. (Filled boxes, protein coding genes; empty boxes, non-coding genes; Ω miRNAs; filled lollipops, methylated regions; empty lollipops, unmethylated regions; black, genes with biparental expression; red, genes expressed from the maternal (mat) chromosome; blue, genes expressed from the paternal (pat) chromosome; grey, silenced gene copies. Arrows above the genes, transcription direction of sense genes; arrows below the genes, transcription direction of anti-sense genes. IC, imprinting control region)
Fig. 2
Fig. 2
The loci GRB10 in 7p12.1 and MEST in 7q32, affected by (segmental) upd(7)mat or chromosomal imbalances in SRS
Fig. 3
Fig. 3
The 11p15.5 cluster can be divided in two functional domains whose imprinting is dependent on distinct imprinting control regions (H19/IGF2: IG DMR and KCNQ1OT1: TSS DMR). Mainly hypomethylation of the KCNQ1OT1: TSS DMR is responsible for SRS
Fig. 4
Fig. 4
Epimutations and mutations in 11p15.5 are also responsible for BWS
Fig. 5
Fig. 5
The imprinted region in 14q32.2, and changes associated with TS14
Fig. 6
Fig. 6
Molecular changes currently known to be associated with KOS14
Fig. 7
Fig. 7
The imprinted region in 15q11.2 and PWS. UBE3A encodes an E3 ubiquitin-protein ligase which is expressed exclusively from the maternal allele in human fetal brain and in adult frontal cortex. The role of ATP10A is unclear
Fig. 8
Fig. 8
Alterations in 15q11.2 in AS
Fig. 9
Fig. 9
Organization and imprinting of the complex GNAS locus at 20q13.22, causing PHP
See this image and copyright information in PMC

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