Angelman Syndrome by

Chromosome 15

eleanorw05 — 2024-08-28 08:26:31 UTC

Chromosome 15 is part of the autosomal genome and contains the gene UBE3A. One chromosome in a pair is inherited from our mother and one is inherited from our father.

Angelman Syndrome (AS)

eleanorw05 — 2024-08-28 08:35:13 UTC

Angelman syndrome is a rare neuro-genetic disorder that is characterised by some degree of loss of function to the UBE3A gene located on chromosome 15 (Angelman Syndrome Foundation n.d.). These changes to UBE3A impact brain development. Some symptoms of AS include:

Early developmental delays around 6- 12 months (both physical and mental)
Small head and wide spaced jaw
Reduced speech
trouble walking and balancing
Easily excitable and sudden outbursts of laughter
Trouble sleeping
Seizures

(Mayo Clinic 2024).

These symptoms can vary in presence and severity depending on the mechanism of inheritance for AS. The most common cause - deletion - generally gives the most severe symptoms (Angelman Syndrome Foundation n.d). Despite this, the life expectancy of those with AS is normal.

Rarely, Angelman syndrome can be inherited and it is best to consult a genetic councillor to explore these matters further.

UBE3A gene

eleanorw05 — 2024-08-28 08:36:00 UTC

The UBE3A gene is located on chromosome 15. It codes for a protein called ubiquitin protein ligase or E3A. E3A is a enzyme that acts as a marker to tag other proteins to be broken down. This protein degradation is a typical and important cell function that removes unnecessary or damaged proteins. This degradation is especially important in neurons because it allows them to adapt over time in response to our experiences. This makes E3A critical for learning and memory (MedlinePlus2022). When the expression of UBE3A is disrupted like in Angelman Syndrome, brain development is inhibited.

Uniparental Disomy (UPD)

eleanorw05 — 2024-08-28 09:04:11 UTC

Normally we inherit one copy of a gene from our mother and one from our father. In Uniparental disomy, two copies can be inherited from only one parent (University of Rochester Medical Center n.d.).

Genomic Imprinting

eleanorw05 — 2024-08-28 09:06:33 UTC

Genomic imprinting is the process by which one copy of a gene, either the maternal or paternal can be 'turned off' or silenced while the other remains active and is expressed (National Human Genome Research Institute 2024).

Maternal imprinting of UBE3A

eleanorw05 — 2024-08-28 09:48:21 UTC

In other body cells, both copies of UBE3A are active. However, in neurons located in the central nervous system, genomic imprinting occurs, resulting in the paternal copy of UBE3A being suppressed (MedlinePlus 2022). This leaves the maternal copy as the expressed gene.

eleanorw05 — 2024-08-28 09:48:33 UTC

The imprinting of UBE3A in neurons, and the loss of function of the active copy in AS, is especially pertinent in determining the symptoms indicative of Angelman syndrome (MedlinePlus 2022).

UPD in Angelman syndrome

eleanorw05 — 2024-08-28 11:01:26 UTC

A small amount of Angelman syndrome cases (for example - approximately 3% of cases in the USA) are a result of UPD (Angelman Syndrome Foundation n.d.). Instead of inheriting both a maternal and paternal copy of UBE3A, these people inherit two paternal copies. Because the paternal UBE3A gene is imprinted, the gene is not expressed and no E3A is synthesised.

Causes of Angelman syndrome

eleanorw05 — 2024-08-28 11:07:18 UTC

Other than UPD, there are a range of other avenues that can culminate in the development of AS. The most prevalent (for example - approximately 70% of cases in the USA) result from a deletion of the maternal copy of the gene UBE3A. This presents a similar outcome to uniparental disomy, where there is no active copy of the gene present to produce the necessary protein product E3A. Other forms of development include mutations to the maternal UBE3A gene itself that inhibit its ability to perform its function and issues with the imprinting process that can make the usually active maternal copy unavailable (Angelman Syndrome Foundation n.d.).