page_title: Angelman syndrome
section_title: Cause and pathophysiology
hierarchical_section_title: Angelman syndrome / Cause and pathophysiology
caption_attribution_description: English: This image is per http://www.ensembl.org/info/about/disclaimer.html.
context_page_description: Angelman syndrome or Angelman's syndrome is a genetic disorder that mainly affects the nervous system. Symptoms include a small head and a specific facial appearance, severe intellectual disability, developmental disability, limited to no functional speech, balance and movement problems, seizures, and sleep problems. Children usually have a happy personality and have a particular interest in water. The symptoms generally become noticeable by one year of age.
  Angelman syndrome is due to a lack of function of part of chromosome 15 inherited from a person's mother. Most of the time, it is due to a deletion or mutation of the UBE3A gene on that chromosome. Occasionally, it is due to inheriting two copies of chromosome 15 from a person's father and none from their mother. As the father's versions are inactivated by a process known as genomic imprinting, no functional version of the gene remains. Angelman syndrome is typically due to a new mutation rather than one inherited from a person's parents. Diagnosis is based on symptoms and possibly genetic testing.
  No cure is available. Treatment is generally supportive in nature. Anti-seizure medications are used in those with seizures.
context_section_description: Angelman Syndrome is caused by the lack of expression of a gene known as UBE3A in developing . This gene is located within a region of chromosome 15 known as 15q11-q13 and is part of the ubiquitin pathway. In fact, UBE3A codes for a very selective E6-AP ubiquitin ligase for which MAPK1, PRMT5, CDK1, CDK4, β-catenin, and UBXD8 have been identified as ubiquitination targets
  Typically, a fetus inherits a maternal copy of UBE3A and a paternal copy of UBE3A. In certain areas of developing brain, the paternal copy of UBE3A is inactivated through a process known as imprinting and the fetus relies on the functioning maternal copy of UBE3A in order to develop normally. In an individual with AS, however, the maternal UBE3A gene is absent or not functioning normally. This can be due to genetic errors such as the deletion or mutation of a segment of chromosome 15, uniparental disomy, or translocation. While Angelman syndrome can be caused by a single mutation in the UBE3A gene, the most common genetic defect leading to Angelman syndrome is a ~4Mb (megabase) maternal deletion in chromosomal region 15q11-13. 
  Specifically, the paternal copy of UBE3A is known to be imprinted within the hippocampus, cortex, thalamus, olfactory bulb, and cerebellum . Therefore, in these areas of the brain, a functioning maternal copy of UBE3A is essential for proper development. 
  Region 15q11-13 is implicated in both Angelman Syndrome and Prader-Willi syndrome (PWS). While AS results from the loss of UBE3A gene within this region on the paternal chromosome, loss of a different cluster of genes within the same region on the maternal chromosome causes PWS.  
  The methylation test that is performed for Angelman syndrome looks for methylation on the gene's neighbor SNRPN, which is silenced by methylation on the maternal copy of the gene.
caption: Chromosome 15
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