Kinnary Patel

Professor: Dr. Derrick Hilton

Short Paper 1
09/16/2014
Introduction

Inheritance

Identification

Gene Function

Conclusion

References

Angelman Syndrome
Angelman syndrome is a severe intellectual disability resulting in ataxia
(movement and balance difficulties), epilepsy, behavioral uniqueness, mental retardation,
and severe speech impairment. The disorder is categorized as a neurodevelopment
disorder as it affects primarily the nervous system. Patients have been described as
having an angel-like demeanor as they are frequently smiling and/or laughing; the
patients have a very happy and excitable personality. Exterior qualities recognized as

having light skin, reduced retinal pigment, low hair bulb tyrosinase activity, and
incomplete melanization of melaonsomes.
Angelman syndrome is caused by mutations in the UBE3A gene. This gene
instructs to make proteins call ubiquitin protein ligase E3A- these proteins ligases are
enzymes that target other proteins to degrade within cells. Proteasomes recognize and the
digest these ubiquitin-tagged proteins. The protein degradation is a normal process that
removes damaged or unnecessary proteins and helps maintain the normal function of the
cells. Studies have shown that UBE3A plays an important role in the normal development
and functions of the nervous system.
There are four genetic mechanisms that can cause AS:
1. 70% result from de novo maternal deletions involving
chromosome 15q11.2-913
2. 2% result from uniparental disomy of 15q11.2-913 where the
child receives two copies of a chromosome from one parent and
no copies from the other parent.
3. 2-3% result from imprinting defects
4. 25% mutations in gene encoding the ubiquitin protein ligase E3A
Figure 1 Illustrates the different type of genetic mechanisms explained in
the genetic disorder. The fourth chromosome shows the genetic mutation
that causes Angelman Syndrome

gene

The main cause of Angelman syndrome is the absence of the maternal copy of the
imprinted UBE3A gene caused by maternal deletions. The deletion region takes place on
chromosome 15 (cytogenic location: 15q11.2), (molecular location on chromosome 15
base pairs: 25,237,224 to 25,439,042).

Figure 2

UBE3A gene is located on the

long (q) arms of chromosome
15 at position 11.2. Any
abnormalities in involving this
region can cause Angelman
syndrome.

References
Wagstaff, J. "Linkage Analysis in Familial Angelman Syndrome." National Institutes of
Health, July 1993. Web. 15 Sept. 2014.

Fang, P. "The Spectrum of Mutations in UBE3A Causing Angelman Syndrome." Human

Molecular Genetics 8.1 (1999): 129-35. PubMed. Web. 15 Sept. 2014.
<http://www.ncbi.nlm.nih.gov/pubmed/9887341?dopt=Abstract>.
Singhmar, Pooja, and Arun Kumar. "Angelman Syndrome Protein UBE3A Interacts with
Primary Microcephaly Protein ASPM, Localizes to Centrosomes and Regulates
Chromosome Segregation." Ed. Hui Zou. PLoS ONE 6.5 (2011): E20397. PubMed. Web.
15 Sept. 2014. <http://www.ncbi.nlm.nih.gov/pubmed/21633703?dopt=Abstract>