Patients diagnosed with Angelman syndrome (AS) frequently meet the diagnostic criteria for ASD (Peters et al., 2004). Angelman syndrome is caused by mutations in or lack of expression of the maternal copy of UBE3A (Kishino et al., 1997; Matsuura et al., 1997), the paternal copy of which is normally silenced in neurons (Albrecht et al., 1997; Rougeulle et al., 1997; Yamasaki et al., 2003). Maternally derived duplications and triplications of a genomic region which contains UBE3A have also been identified in patients with non-syndromic ASDs (Cook et al., 1997; Glessner et al., 2009; Hogart et al. 2010). The protein encoded by UBE3A is the ubiquitin-protein ligase (UBE3A), also known as E6AP ubiquitin-protein ligase (E6AP; Huibregtse et al., 1993). The ubiquitin-proteasome degradation system has been implicated in synapse function and plasticity (reviewed in Mabb and Ehlers, 2010).
