Peripheral UBE3A expression as a predictor of the clinical phenotype in Angelman Syndrome

Summary This project will utilise many of the developed technologies and clinical data to characterise relationships between UBE3A expression with objective assessments of developmental functioning, autism traits, and sleep problems.

Project Details

Angelman Syndrome (AS) is characterised by varying degrees of intellectual disability (ID), autism ASD traits, severe seizures, motor and sleep problems. AS is caused by severe reduction in the expression of UBE3A in the brain. Despite the systemic pattern of reduction of UBE3A in AS, much research has been focused on the central nervous system, in animal models. Until now, comprehensive analysis of UBE3A expression in peripheral tissues and different clinical phenotypes have not been performed in humans.    Over the past 3 years our team at MCRI has led a study that aims to better characterise the molecular basis of AS presentations and the variability between affected individuals. Thirty participants with AS have been recruited and assessed with a number of neuropsychological assessments as well as novel experimental methods. Extensive behavioural and parent-reported medical history data, as well as bio-specimens including DNA, RNA and protein lysates have been collected from various tissue types for most participants. Genetic and genomic state-of-the-art technologies have also been developed to accurately detect changes at epigenetic, RNA and protein levels.     This project will utilise many of the developed technologies and clinical data to characterise relationships between UBE3A expression with objective assessments of developmental functioning, autism traits, and sleep problems. Twenty new patients will be recruited and assessed as part of this project. Additionally, patients who have previously been involved in our studies will be recontacted to undertake further assessment. This additional time-point will help us to better define relationships between the neurodevelopmental and epigenetic trajectories in individuals with AS. This study will provide an indication of the associations between UBE3A molecular changes and clinical phenotypes of AS, to assist in better understanding disease natural history. The findings may also have implications for patient stratification in clinical trials aimed at improving outcomes for AS individuals.