Facts About Angelman Syndrome: The Genetic Mutations that Cause Angelman Syndrome

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Symptoms of Angelman Syndrome

Characteristic symptoms of Angelman syndrome include speech difficulties, developmental delay (which is noticeable from about 6-12 months), seizures, trouble with balance and walking, sleep disturbance, and frequent smiling. The name comes from Dr. Harry Angelman who first described the condition in 1965. Children with Angelman syndrome have at one time been called “puppet children,” because Angelman noted a similarity between some of his patients and a painting he saw in Verona called “Boy with a Puppet.” The term is no longer used as it is seen as stigmatizing.

Angelman syndrome affects 1 in every 12,000 to 20,000 live births.

Angelman Syndrome Genetics

The genetic mutation at the heart of the condition is on a gene called UBE3A which is found on chromosome 15. We each have two copies of this gene, one that we inherit from our mother and one from our father. In patients with Angelman syndrome it is only the maternal version of the UBE3A gene that is affected. Both maternal and paternal UBE3A are active in most cells and tissues of the body, however in some areas of the brain it is only the maternal version that is active. An umbrella term for this is imprinting, where a gene is expressed based on parental origin.

If there is a fault or defect with this maternal version it can mean that some brain regions have no active UBE3A gene, and that’s where the problems start. UBE3A codes for an enzyme, ubiquitin protein ligase E3A. The loss of function of this enzyme causes many of the problems associated with Angelman syndrome.

There are several different types of UBE3A genetic mutations:

  • Chromosomal deletion - this is the biggest cause of Angelman syndrome where a whole section of the chromosome, including UBE3A is deleted. Therefore, there is no gene at all.
  • Paternal disomy - there are two copies of the paternal chromosome 15, and none of the maternal version. As it is only the maternal version of the Angelman gene that is expressed in the brain, Angelman syndrome will occur.
  • Mutations of UBE3A gen****e - small genetic mutations cause the maternal version of the gene to malfunction.
  • Imprinting Centre Problems - a small region of DNA near the UBE3A gene is called the imprinting centre and it controls whether the gene is switched on or off. Abnormalities in the maternally derived imprinting centre can cause Angelman syndrome.

For the most part Angelman syndrome is not inherited as most of the changes occur either during early embryonic development or in the production of sperm and eggs cells. Most affected individuals do not have a family history of the problem.