Show Summary Details
Page of

UBE3A and the Angelman Syndrome 

UBE3A and the Angelman Syndrome
Chapter:
UBE3A and the Angelman Syndrome
Author(s):

Charles A. Williams

DOI:
10.1093/med/9780199934522.003.0162
Page of

PRINTED FROM OXFORD MEDICINE ONLINE (www.oxfordmedicine.com). © Oxford University Press, 2021. All Rights Reserved. Under the terms of the licence agreement, an individual user may print out a PDF of a single chapter of a title in Oxford Medicine Online for personal use (for details see Privacy Policy and Legal Notice).

date: 24 February 2021

Angelman syndrome (AS) is a neurodevelopmental disorder caused by deficiency of the ubiquitin-protein ligase, UBE3A, in the brain. UBE3A shows parent-specific differential expression, or imprinting, limited to brain and spinal cord neurons (glial cells are not imprinted). In non-CNS tissues, the maternal and paternal alleles of UBE3A are biallelically expressed. AS results from several genetic mechanisms that disrupt the functional allele of UBE3A inherited from the mother; absence of a functional paternal allele of UBE3A causes no phenotypic effects. Clinical features involve the combination of severe intellectual deficiency, seizures, absent speech, hypermotoric and ataxic movements, happy demeanor and hypermotoric behaviors. Accurate diagnosis rests on a combination of clinical criteria and molecular and/or cytogenetic testing. Analysis of parent specific DNA methylation imprints in the critical 15q11.2-q13 genomic region identifies 75 to 80% of all individuals with the syndrome, including those with cytogenetic deletions, imprinting center defects and those with paternal uniparental disomy (UPD). The landscape of UBE3A cellular effects is immense as the protein has multiple targets and protein associations. Some of these effects are directly related to its established role in ubiquitination of proteins targeted for proteasome degradation but additional effects may involve other types of protein regulation and gene transcriptional effects. These new discoveries help clarify some of neural plasticity deficits seen in AS.

Access to the complete content on Oxford Medicine Online requires a subscription or purchase. Public users are able to search the site and view the abstracts for each book and chapter without a subscription.

Please subscribe or login to access full text content.

If you have purchased a print title that contains an access token, please see the token for information about how to register your code.

For questions on access or troubleshooting, please check our FAQs, and if you can't find the answer there, please contact us.