Angelman syndrome (AS), UBE3NE6-AP, was not identified until very recently, although this gene had previously been mapped to within the PWS/AS candidate region 1. In contrast to the PWS (Prader-Willi syndrome) candidate genes, the link between UBE3A and AS was established not on the basis of the allele-specific (maternal) expression of UBE3A but on the discovery of UBE3A mutations in some of the AS patients without deletion, uniparental disomy or imprinting mutation2• 3• The first case studied was a 15q inversion inherited by an AS child from her normal mother and found to disrupt the 5'end of UBE3A2. 4. In addition to this patient, four other AS cases have been found to be heterozygous for point mutations. Two are small deletions and insertions (duplication) that cause a frame-bp