Causes of Angelman Syndrome
Angelman Syndrome (AS) is a rare genetic disorder that primarily affects the nervous system. It is characterized by developmental delays, intellectual disabilities, speech impairments, and a unique behavioral phenotype. AS is caused by various genetic abnormalities that disrupt the normal functioning of a specific gene called UBE3A.
1. Deletion of the UBE3A gene:
The most common cause of Angelman Syndrome is the deletion of a segment of genetic material on the maternally inherited chromosome 15. This deletion occurs in approximately 70% of individuals with AS. The missing genetic material includes the UBE3A gene, which is responsible for producing a protein called ubiquitin ligase E3A. This protein plays a crucial role in regulating the function of other proteins in the brain.
2. Uniparental disomy:
In about 2-5% of Angelman Syndrome cases, individuals inherit both copies of chromosome 15 from their father instead of one from each parent. This phenomenon is known as uniparental disomy (UPD). In these cases, the UBE3A gene is present, but its expression is silenced in the brain due to the imprinting process. Imprinting is a mechanism that determines which copy of a gene is active based on its parental origin.
3. UBE3A gene mutation:
In a small percentage of Angelman Syndrome cases (around 11%), individuals have a mutation within the UBE3A gene itself. These mutations can disrupt the normal function of the UBE3A protein, leading to the characteristic features of AS. Some mutations may result in a partial loss of UBE3A function, while others may completely abolish its activity.
4. Imprinting center defects:
Imprinting center defects occur in a small number of Angelman Syndrome cases. These defects disrupt the normal regulation of gene expression on chromosome 15. As a result, the UBE3A gene is not properly activated in the brain, leading to the development of AS symptoms.
5. Other rare causes:
In rare instances, Angelman Syndrome can be caused by other genetic abnormalities, such as chromosomal rearrangements or mutations in genes involved in the regulation of UBE3A. These cases account for a very small proportion of individuals with AS.
It is important to note that Angelman Syndrome is not caused by any environmental factors or parental behaviors. The genetic abnormalities responsible for AS occur spontaneously and are not inherited from the parents.
In conclusion, Angelman Syndrome is primarily caused by the deletion of the UBE3A gene, uniparental disomy, UBE3A gene mutations, imprinting center defects, or other rare genetic abnormalities. These genetic abnormalities disrupt the normal functioning of the UBE3A gene, leading to the characteristic symptoms and features of Angelman Syndrome.