Imprinting Disorders


Genomic imprinting is an example of epigenetic inheritance in which differences in gene function depend on whether the allele was inherited from the mother or father. Many disorders appear to involve epigenetic alterations to imprinted genes. Genes involved in imprinting play important roles in both pre‐ and post‐natal growth and neurodevelopment. Imprinting disorders include several childhood genetic disorders such as Prader–Willi, Angelman and Beckwith–Wiedemann syndromes, as well as several types of cancer including Wilms tumour. Recent evidence suggests a correlation between assisted reproductive technologies (ART) and imprinting disorders, a phenomenon requiring more in‐depth studies as the prevalence of ART is increasing. The mechanism of normal imprinting as well as its perturbation in disease is becoming understood and amenable to experimentation.

Key Concepts:

  • Imprinted genes are expressed in a parent‐of‐origin‐dependent manner. Imprinting disorders result from genetic abnormalities in imprinted genes.

  • Approximately 1% of the human genome is imprinted, a process which occurs during gamete development.

  • Imprinted genes are generally associated with growth, neurodevelopment and epigenetics.

  • The first imprinted genes discovered were IGF2 (paternally expressed) and H19 (maternally expressed), both located at 11p15.

  • There is an imprinted gene cluster located at 15q11–q13, associated with Prader–Willi and Angelman syndromes. Imprinted genes/transcripts within this region include NDN, MAGEL2, SNURF‐SNRPN, SNORD116, SNORD115 and UBE3A.

  • Well‐characterised imprinting disorders include Prader–Willi syndrome (PWS), Angelman syndrome (AS), Beckwith–Wiedemann syndrome (BWS), Albright hereditary osteodystrophy (AHO), pseudohypoparathyroidism (PHP), Silver–Russell syndrome (SRS) and transient neonatal diabetes mellitus (TNDM).

  • Imprinted genes are associated with many types of cancers, primarily due to a process called loss of imprinting (LOI) which leads to aberrant gene expression. Cancers known to be associated with imprinted genes include Wilms tumour in children, and adult cancers of the ovary, lung, colon and liver.

  • The relationship between artificial reproductive technology (ART) and imprinting disorders is currently being investigated. There is evidence to support a correlation between ART and imprinting disorders which result from loss of maternally imprinted genes such as AS and BWS.

Keywords: imprinting; imprinting disorders; gene methylation; Prader–Willi syndrome; Angelman syndrome; Beckwith–Wiedemann syndrome; uniparental disomy; assisted reproductive technology

Figure 1.

Types and mechanisms of uniparental disomy.

Figure 2.

Chromosome 11 ideogram illustrating 11q15.5, the imprinted region critical in BWS, SRS and several types of cancer.

Figure 3.

Chromosome 15 ideogram illustrating 15q11–q13, the imprinted region critical in PWS and AS.



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Further Reading

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Weaver JR, Susiarjo M and Bartolomei MS (2009) Imprinting and epigenetic changes in the early embryo. Mammalian Genome 20(9–10): 532–543.

Web Links

Angelman Syndrome; MIM number:105830 OMIM.

Beckwith–Wiedemann Syndrome; MIM number:130650 OMIM.

Cyclin‐dependent Kinase Inhibitor 1C (p57, Kip2) (CDKN1C); Locus ID: 1028. LocusLink:

Cyclin‐dependent Kinase Inhibitor 1C (p57, Kip2) (CDKN1C); MIM number: 600856. OMIM:‐post/Omim/dispmim?600856

GNAS Complex; MIM number: 139320. OMIM:

H19, Imprinted Maternally Expressed Untranslated mRNA (H19); Locus ID: 8043. LocusLink:

H19, Imprinted Maternally Expressed Untranslated mRNA (H19); MIM number: 103280. OMIM:‐post/Omim/dispmim?103280

Insulin‐like Growth Factor 2 (Somatomedin A) (IGF2); Locus ID: 3481. LocusLink:

Insulin‐like Growth Factor 2 (somatomedin A) (IGF2); MIM Number: 147470. OMIM:‐post/Omim/dispmim?147470

KCNQ1 Overlapping Transcript 1 (KCNQ1OT1); Locus ID: 10984. LocusLink:

KCNQ1 Overlapping Transcript 1 (KCNQ1OT1); MIM number: 604115. OMIM:‐post/Omim/dispmim?604115

KQT‐like Subfamily, Member 1 (KCNQ1); Locus ID: 3784. LocusLink:

KQT‐like Subfamily, Member 1 (KCNQ1); MIM number: 192500. OMIM:‐post/Omim/dispmim?192500

Prader–Willi Syndrome; MIM number:176270. OMIM:

Pseudohypoparathyroidism; MIM number:103580 OMIM:

Silver–Russell Syndrome; MIM number:180860 OMIM:

The Medical Research Council International Centre for Mouse Genetics Imprinting Maps.

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Henkhaus, Rebecca S, Feinberg, Andrew P, Niemitz, Emily L, and Butler, Merlin G(Sep 2011) Imprinting Disorders. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0005477.pub2]