UBE3A and Global developmental delay: In addition, loss of function in a number of E3 enzymes has been shown to have an important role in the development of severe physiological conditions such as certain cancers and neurological disorders.3 A representative instance of the latter is Angelman syndrome (AS), a severe neurodevelopmental disorder, with clinical features of mental retardation, developmental delay, ataxia and epilepsy.4, 5 The principal protein affected in AS is the E3 ubiquitin ligase E6-associated protein (E6AP/UBE3A), the gene being found on chromosome 15q11-13.