Mutation screening of the UBE3A/E6-AP gene in autistic disorder

Previous reports of individuals with autistic disorder with maternal duplic ations of 15q11-q13,(1-11) the Prader-Willi/Angelman syndrome region, sugge st this area as a source of candidate genes in autistic disorder. Maternal truncation mutations in UBE3A, which encodes for E6-AP ubiquitin-protein li gase, have been shown to cause Angelman syndrome,(12,13) which can also res ult from the absence of maternal chromosomal material from this region. Des pite showing no evidence for imprinting in other tissues, this gene was rec ently discovered to be preferentially maternally expressed in human brain(1 4,15) and expressed solely from the murine maternal chromosome in the hippo campus and cerebellar Purkinje cells,(16) regions implicated in the neuropa thology of autism.(17-20) Based on this evidence, the coding region and a p utative promoter region were sequenced in ten autistic subjects, Several po lymorphisms were detected, but no evidence was found for a functional mutat ion. Evidence for likely altered regulation of UBE3A expression in maternal 15q11-q13 duplications suggests further investigation of the regulatory re gions of this gene in autistic disorder.