*The picture in the header was taken from here.
This web page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison.
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What is Angelman syndrome?
It is a neurodevelopmental disorder,where patients usually show signs of intellectual and development delay, difficulties in balance and movement, epilepsy, sleep disturbance, frequent laughter, and a small head size (microcephaly) [1,6].
How common is Angelman syndrome?
AS has affected people of various racial groups throughout the world. In North America, most patients are of Caucasian origin. A Swedish study showed that AS has a prevalence of 1/12,000 while another Danish study reported that it has a prevalence of about 1/10,000. [3].
What causes Angelman syndrome?
Angelman syndrome is caused by the loss of function of the gene UBE3A [1,5]. A normal person usually inherits 1 copy of the UBE3A gene from each parent and both genes are active in most tissues [1]. However, in the brain, due to genomic imprinting, only the maternal allele of the UBE3A gene is expressed [1]. If this maternal allele is missing or defective, it will lead to Angelman syndrome.
Figure 1: The locus of the UBE3A gene on chromosome 15. Diagram taken from Genetics Home Reference
UBE3A
The UBE3A gene is located on the long (q) arm of chromosome 15 at position 11.2. It expands from base pair 25,582,395 to base pair 25,684,174, totaling to 101,779 base pairs [2].
UBE3A gene encodes for a protein called ubiquitin protein ligase E3A, which marks other proteins that need to be degraded with ubiquitin [2]. Proteasomes, a protein complex, recognize these proteins that are tagged with ubiquitin and break them down [2]. Therefore, ubiquitin protein ligase E3A is important in getting rid of damaged and useless proteins, and maintaining cellular functions [2]. However, how this protein functions in the nervous system and how a defective E3A protein leads to Angelman syndrome is not fully known yet [2].
About 70-75% of this syndrome is due to a 4Mb deletion in the chromosomal region, which encompasses the UBE3A gene [5]. This deletion usually happens de novo because there are repetitive DNA sequences which cause chromosomes to not align well [5]. On the other hand, paternal uniparental disomy of chromosome 15, where the patient inherits 2 copies of chromosome 15 from the father, accounts for 2-3% of cases [5]. About 3-5% of cases are due to errors in the imprinting process within the 15q11-q13 region, which causes the inactivation of the maternal copy [5]. 5-10% of cases are due to point mutations in the UBE3A gene while the causes of the remaining 10% remain unknown [1].
The UBE3A gene is located on the long (q) arm of chromosome 15 at position 11.2. It expands from base pair 25,582,395 to base pair 25,684,174, totaling to 101,779 base pairs [2].
UBE3A gene encodes for a protein called ubiquitin protein ligase E3A, which marks other proteins that need to be degraded with ubiquitin [2]. Proteasomes, a protein complex, recognize these proteins that are tagged with ubiquitin and break them down [2]. Therefore, ubiquitin protein ligase E3A is important in getting rid of damaged and useless proteins, and maintaining cellular functions [2]. However, how this protein functions in the nervous system and how a defective E3A protein leads to Angelman syndrome is not fully known yet [2].
About 70-75% of this syndrome is due to a 4Mb deletion in the chromosomal region, which encompasses the UBE3A gene [5]. This deletion usually happens de novo because there are repetitive DNA sequences which cause chromosomes to not align well [5]. On the other hand, paternal uniparental disomy of chromosome 15, where the patient inherits 2 copies of chromosome 15 from the father, accounts for 2-3% of cases [5]. About 3-5% of cases are due to errors in the imprinting process within the 15q11-q13 region, which causes the inactivation of the maternal copy [5]. 5-10% of cases are due to point mutations in the UBE3A gene while the causes of the remaining 10% remain unknown [1].
Figure 2: The various mutations in chromosome 15 that lead to Angelman syndrome. Diagram taken from Angelman Syndrome Foundation
Can Angelman syndrome be inherited?
Most patients do not inherit this disorder. This is because deletion in the maternal chromosome 15 or paternal uniparental disomy happens randomly during the development of reproductive or embryonic cells [1].
However, in certain cases where there are mutations in the UBE3A gene or in nearby region that controls gene activation, it could still be possible that this syndrome is inherited [1].
Are there any treatments?
Unfortunately, no treatment has been found yet [4]. To control epilepsy, one can use various types of anticonvulsant medications but one problem to this is that there are various types of seizures and it is hard to ascertain what types of medication is needed [4]. To help with sleeping conditions, most families use melatonin [4]. Some patients undergo various therapies such as physiotherapy, occupational therapy, speech therapy and music therapy to help improve their condition [4].
Most patients do not inherit this disorder. This is because deletion in the maternal chromosome 15 or paternal uniparental disomy happens randomly during the development of reproductive or embryonic cells [1].
However, in certain cases where there are mutations in the UBE3A gene or in nearby region that controls gene activation, it could still be possible that this syndrome is inherited [1].
Are there any treatments?
Unfortunately, no treatment has been found yet [4]. To control epilepsy, one can use various types of anticonvulsant medications but one problem to this is that there are various types of seizures and it is hard to ascertain what types of medication is needed [4]. To help with sleeping conditions, most families use melatonin [4]. Some patients undergo various therapies such as physiotherapy, occupational therapy, speech therapy and music therapy to help improve their condition [4].
Famous Angelman syndrome patients
James Farrell, son of Hollywood actor Colin Farrell is an Angelman syndrome patient [4].
Here, Colin Farrell talks about his son's condition of Angelman Syndrome:
Retrieved from YouTube, 2011. Colin Farrell Talks About His Son's Condition, Angelman Syndrome.
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Professional baseball player Dave Henderson, professional hockey player Peter McDuffe and writer Ian Rankin also have sons with Angelman syndrome [4].
References:
[1] Genetics Home Reference - Angelman syndrome
[2] Genetics Home Reference - UBE3A
[3] Angelman Syndrome Foundation
[4] News medical
[5] Beleza-Meireles, A., Cerqueira, R., Sousa, S. B., Palmeiro, A., Ramos, L. (2011). Novel deletion encompassing exons 5-12 of the UBE3A gene in a girl with Angelman syndrome. European Journal of Medical Genetics, 54(3):348-350. doi:10.1016/j.ejmg.2011.02.010.
[6] Horsthemke, B., Wawrzik, M., Groß, S., Lich, C., Sauer, B., Rost, I., Krasemann, E., Kosyakova, N., Liehr, T., Weise, A., Dybowski, J. N., Hoffmann, D., Wieczorek, D. (2011). Parental origin and functional relevance of a de novo UBE3A variant. European Journal of Medical Genetics, 54(1):19-24. doi:10.1016/j.ejmg.2010.09.005
[1] Genetics Home Reference - Angelman syndrome
[2] Genetics Home Reference - UBE3A
[3] Angelman Syndrome Foundation
[4] News medical
[5] Beleza-Meireles, A., Cerqueira, R., Sousa, S. B., Palmeiro, A., Ramos, L. (2011). Novel deletion encompassing exons 5-12 of the UBE3A gene in a girl with Angelman syndrome. European Journal of Medical Genetics, 54(3):348-350. doi:10.1016/j.ejmg.2011.02.010.
[6] Horsthemke, B., Wawrzik, M., Groß, S., Lich, C., Sauer, B., Rost, I., Krasemann, E., Kosyakova, N., Liehr, T., Weise, A., Dybowski, J. N., Hoffmann, D., Wieczorek, D. (2011). Parental origin and functional relevance of a de novo UBE3A variant. European Journal of Medical Genetics, 54(1):19-24. doi:10.1016/j.ejmg.2010.09.005
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If you find my website helpful, please consider donating to the Foundation for Angelman Syndrome Therapeutics (FAST)
Created by Jonathan Mok
[email protected]
Last updated 02/23/2012
Genetics 677
Created by Jonathan Mok
[email protected]
Last updated 02/23/2012
Genetics 677