Angelman's syndrome research

In 3% to 7% of cases,Angelman syndrome occurs when a person has two copies of the paternal chromosome 15 instead of one copy from each parent. This phenomenon is called paternal uniparental disomy (UPD). People with paternal UPD for chromosome 15 have two copies of the UBE3A gene, but they are both inherited from the father and are therefore inactive in the brain.

 In neurons, the paternal allele of UBE3A is intact but epigenetically silenced, raising the possibility that Angelman syndrome could be treated by activating this silenced allele to restore functional UBE3A protein. Using an unbiased, high-content screen in primary cortical neurons from mice, University of North Carolina identified twelve topoisomerase I inhibitors and four topoisomerase II inhibitors that unsilence the paternal Ube3aallele. These drugs included topotecan, irinotecan, etoposide and dexrazoxane (ICRF-187). At nanomolar concentrations, topotecan upregulated catalytically active UBE3A in neurons from maternal Ube3a-null mice. 

• Developmental delay, functionally severe
• Speech and language impairment, lack of speech or minimal use of words
• Receptive and nonverbal communication skills higher than verbal ones
• Movement or balance disorder, usually ataxia of gait and/or tremulous movement of limbs
• Behavioral uniqueness: any combination of frequent laughter/smiling; apparent happy demeanor; easily excitable personality, often with hand flapping movements;hypermotoric behavior; short attention span

Angelman syndrome is a genetic disorder. It's most often caused by problems with a gene located on chromosome 15 called the ubiquitin-protein ligase E3A (UBE3A) gene.Genes are segments of DNA that provide the blueprints for all of your characteristics. You receive your genes, which occur in pairs, from your parents. One copy comes from your mother (maternal copy), and the other copy comes from your father (paternal copy).Both genes in a pair usually are active. This means that your cells use information from both the maternal copy and the paternal copy of each gene pair. But in a small number of genes, only one copy of a gene pair is active. The activity of each gene copy depends on whether it was passed from your mother or from your father. This parent-specific gene activity is called imprinting. In these genes, when the copy that's usually active is missing or defective, it causes problems in the functions and characteristics controlled by that gene.