History & Discovery: Dr. Harry Angelman’s Observations, (2) Special Issues of Adolescence and The Transition to Adulthood
Louis Tiranoff and Jill Clayton-Smith (1) – New York
Visual media plays a powerful role in helping families and others understand the natural history and many of the day-to-day concerns that parents have for their children and adults with AS. This work combines the skills of individuals experienced with the behavioral and clinical problems of AS with the talents of someone able to produce audiovisual and other types of transferable media. This project developed DVDs and other communication formats to enable others to actually see children and adults with AS in many different home and living situations.
Sleep Patterns and Autistic Symptomology in Angelman Syndrome: Further Delineation of the Behavioral Phenotype
Nicolay Walz – Cincinnati Children’s Hospital
ASF maintains contact with hundreds of families throughout the United States and in other parts of the world and this contact serves as a valuable resource for investigators wishing to learn more about certain behavioral or medical problems of those with AS. In this project, information was gleaned from over 300 families who provided questionnaire data about the sleep difficulties present in their child with AS. Results from this questionnaire confirmed that a variety of sleep problems do exist in AS. These sleep difficulties range from easily awakening by noise, reliance on sleep facilitators, poor sleep initiation, and short sleep duration.
Molecular Genetic Analysis of the Drosophila Angelman Syndrome Gene
UBE3A, the gene when disrupted causes AS, is present in all animal and insect species, thus indicating how important it is for normal neuronal function. These investigators were able to identify the equivalent of the UBE3A gene in Drosophila, the fruit fly, and were able to manipulate it and change the expression of UBE3A in such a way that they learned more about other proteins that interact with the Drosophila equivalent of UBE3A. This interaction of other proteins proved to be important in understanding how UBE3A normally acts within brain cells and what happens to brain cells when UBE3A is disrupted.
A Therapeutic Trial of Folate and Betaine in Angelman Syndrome
Arthur Beaudet – Baylor College of Medicine
One of the unique aspects of the brain problem in AS is that only the UBE3A on the maternally inherited number 15 chromosome is disrupted. The other UBE3A, located on the paternally derived chromosome, is silenced by a control mechanism that involves changes in the DNA and its surrounding proteins. These changes are influenced by differences in their “methylation” status. Methyl molecules (e.g., with the chemical formula of CH3) are important regulators of gene action. ASF has supported attempts to change the methylation status of the UBE3A by providing dietary supplements that increased methyl availability. Two of these agents are folic acid and trimethylamine (Betaine) and this was the earliest human drug trial ever conducted on AS. The result showed minimal benefit of this type of therapy but the study laid the foundation for future therapeutic trials.