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Genotypes of Angelman syndrome

A genotype is the underlying genetic difference that is causing AS. There are 5 genotypes of Angelman syndrome

What does “genotype” mean in Angelman Syndrome?

Angelman syndrome (AS) is caused by a genetic difference that affects the UBE3A gene, resulting in not enough or less functional UBE3A protein in the brain. There are multiple different mechanisms that affect the UBE3A gene and cause the absence or reduction of UBE3A protein. In Angelman syndrome, we call these different genetic mechanisms “genotypes.”

The Angelman syndrome genotypes

Neurotypical*

*For comparison, not a genotype
In neurotypical individuals who do not have Angelman syndrome, the UBE3A gene from the egg is turned on in neurons, while the UBE3A gene from the sperm is turned off.

Deletion (70%)

The most common cause of Angelman syndrome is a deletion, or missing section on the chromosome 15 that came from the egg. This missing section includes the UBE3A gene plus about 10 other genes. When the maternal UBE3A gene is missing and the paternal UBE3A gene is turned off, no UBE3A is made in the neurons.
Learn more about Deletion AS

Mutation (10%)

Mutations within the UBE3A gene from the egg cause about 10-15% of AS. A mutation is a difference or variant within the DNA that results in no UBE3A protein or UBE3A protein that is less functional or nonfunctional.
Learn more about Mutation AS

Uniparental Disomy (UPD) (~5%)

UPD AS happens when both copies of chromosome 15 came from the sperm. Because the paternal UBE3A gene is always turned off in neurons, when both copies of chromosome 15 come from the sperm, both UBE3A genes are turned off, and no UBE3A protein is made in the brain.
Learn more about UPD AS

Imprinting Center Defect (ICD) (~2-3%)

An imprinting center defect (ICD) is when the maternal imprinting center does not work correctly, and as a result the maternal UBE3A gene is incorrectly turned off. Because the paternal UBE3A gene is always turned off in neurons, an ICD on the maternal chromosome 15 results in no UBE3A protein being made. ICDs can be caused by a deletion of the AS imprinting center or an error at the AS imprinting center.
Learn more about ICD AS

Mosaic (1%)

When the genetic difference that causes AS occurs after fertilization, during the development of an embryo, the person lives with Mosaic AS. A person living with Mosaic AS has some cells that make UBE3A and some cells that do not make UBE3A in their body.
Learn more about Mosaic AS

Does your loved one have a clinical diagnosis of AS?

Historically, about 10% of people diagnosed with  Angelman syndrome had a “clinical diagnosis”, meaning that even though the person did not have a known genetic difference, that person had enough characteristics of Angelman syndrome that they were considered to have AS. More recently, most individuals with a clinical diagnosis of AS have been found to have a genetic difference in other genes, and actually live with different but similar genetic conditions.  

If a loved one has a clinical diagnosis of AS but has not had genetic testing in the past decade (or ever), seeking updated genetic testing may provide clarity. For assistance, reach out to FAST’s genetic counselor at genetic.counselor@cureangelman.org.

Are there clinical trials for individuals living with Angelman syndrome?

Currently, there are active human clinical trials for deletion, mutation, UPD, and ICD genotypes. For the most up-to-date information, please visit our Clinical Trial finder to better understand your loved one’s eligibility.

Questions about genotypes?

FAST’s genetic counselor, Niki Armstrong, can help you better understand your loved one’s genotype and what it means for your family.
Schedule a 1:1 Appointment

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