Angelman Syndrome Research Paper

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Pages: 7

Angelman syndrome (AS) is a neurodevelopmental disorder with a strong genetic component, which can cause symptoms as severe as mental retardation and epilepsy. Signs and symptoms are not shown until 6-12 months. Developmental delays such as lack of speech production (babbling) and motor impairments (crawling) can be seen. Throughout adulthood, other symptoms may develop such as intellectual disability, frequent smiling, and ataxia. AS is also known has the Happy Puppet syndrome due to excessively happy behavior which is explained in psychosocial Kinship model (Gasca et al. 2010) AS is rare and usually occurs in about 1 to 12,000 babies. There is no cure for AS but the symptoms can be managed with the patient having a more than likely chance …show more content…
DNA methylation and demethylation are processes that occur in epigenetics, controlling gene expression. If the gene is more methylated the DNA is harder to access and gets transcribed less. In this class of patients, there are no mutations in the genes, just a defect in the imprinting mechanism, which accounts for 3-5% of the cases (Clayton-Smith et al. 2003) The final classification of AS with a genetic component is Class IV. These patients have mutations in the UBE3A gene. This is crucial because it the enzyme signals proper protein degradation. In a popular knockout mice study for UBE3A, it was shown that maternal negative heterozygous mice exhibited reduced brain weight, ataxia, motor impairment, and abnormal EEG pattern. The heterozygous KO mice exhibited long-term potentiation impairments (Jiang 1998). A final class of AS patients have no known genetic component and are thought to be heterogeneous with other diseases such as Rett Syndrome (Clayton-Smith et al. …show more content…
A major symptom of Angelman Syndrome is microcephaly, which is an abnormal sized brain due to improper brain development. A recent study by Yale found a connection between the Zika virus and how it causes microcephaly. They found that the Zika virus affects mitosis of the neural progenitor cells and surrounding radial glia. (Onorati et al., 2016) In particular, the virus depleted the amount of centrosomes and phospho-TBK-1 a protein found in the mitochondria. Ultimately, the affected mitosis of progenitor stem cells resulted in lack of differentiated neurons causing microcephaly. I would try to determine if the lack of E6-AP causes a disruption of the notch/delta pathway. Using a mice model I would KO the UBE3A gene. I would see whether the KO mice compared to wild type showed difference in neuron differentiation in the rostral migratory stream. I would look at the differences in neurons by staining with NGF. Also, since the sub-ventricular zone in rodents is a source of proliferating stem cells I would use immunofluorescence to tag EGF and FGF-2, two common factors shown to increase proliferation of neural stem cells (Lie et al., 2004). I would also look for decreased expression of the phospho-TBK-1 protein identified in the Yale paper. This could be a possible explanation to why microcephaly is a symptom of Angelman