Understanding the Genetics of Angelman Syndrome

Angelman syndrome is a rare neurological disease characterized by physical and mental developmental delays, among other symptoms. The disease affects about 1 in 12,000 to 20,000 people.

Most cases of Angelman syndrome occur as a result of a random genetic mutation. However, a small number of cases are inherited. In families in which Angelman syndrome is inherited, cases occur approximately 1% more frequently than in the general population.

If your child has been diagnosed with Angelman syndrome, you may have questions about the genetic causes of the disease. Your child’s doctor and a genetic counselor can help you better understand your child’s specific genetic mutation.

How mutations cause Angelman syndrome

Angelman syndrome is caused by the loss of function of the ubiquitin protein ligase E3A (UBE3A) gene located on chromosome 15. Most cases are the result of mutations in this gene or deletions of portions of chromosome 15 that contain this gene. A small number of cases occur due to an unknown cause.

The enzyme that the UBE3A gene encodes for adds a “tag” called ubiquitin to proteins to mark them for recycling. This is one of the ways that cells control which proteins are active in cells and when. The UBE3A enzyme can help the cell to clear a protein that’s damaged or no longer needed.

Development is an important process regulated by many genes, and requires precise control of proteins. When the UBE3A gene malfunctions, certain tissues don’t develop normally. Without the UBE3A enzyme, proteins may be active when they shouldn’t be because cells have trouble getting rid of them when they’re no longer needed.

How gene copies affect Angelman development

Humans have 23 pairs of chromosomes that contain genes. With some exceptions, a person inherits one copy of each gene from their mother and one copy from their father. These maternal and paternal gene copies can be active in different cells.

There are tissues in the brain in which the paternal copy of the UBE3A gene is “switched off” and only the maternal copy is active. If that maternal copy is mutated, those tissues do not have any functional UBE3A enzyme, and the child will develop Angelman syndrome.

Very rarely, a child can inherit two paternal copies of the UBE3A gene, both of which will be inactive in those regions of the brain. This is called uniparental disomy.

Unknown genetic causes

In about 10% of Angelman syndrome cases, there is no known genetic cause. This suggests that other genes may also play a role in the development of the disease, or that other genes act on UBE3A and regulate its activity.

Other chromosome changes may also be having an effect on UBE3A function. This is a relatively new field, but scientists know that many genes regulate each other through contact with different regions of the genome. If a gene that regulates UBE3A is mutated or damaged, it may change how and when UBE3A is active.

Last updated: April 13, 2020

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Angelman Syndrome News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.