MUTATION ANALYSIS OF UBE3A IN ANGELMAN-SYNDROME PATIENTS

Angelman syndrome (AS) is caused by chromosome 15q11-q13 deletions of maternal origin, by paternal uniparental disomy (UPD) 15, by imprintin g defects, and by mutations in the UBE3A gene. UBE3A encodes a ubiquit in-protein ligase and shows brain-specific imprinting. Here we describ e UBE3A coding-region mutations detected by SSCP analysis in 13 AS ind ividuals or families. Two identical de novo 5-bp duplications in exon 16 were found. Among the other 11 unique mutations, 8 were small delet ions or insertions predicted to cause frameshifts, 1 was a mutation to a stop codon, 1 was a missense mutation, and 1 was predicted to cause insertion of an isoleucine in the hect domain of the UBE3A protein, w hich functions in E2 binding and ubiquitin transfer. Eight of the case s were familial, and five were sporadic. In two familial cases and one sporadic case, mosaicism for UBE3A mutations was detected: in the mot her of three AS sons, in the maternal grandfather of two AS first cous ins, and in the mother of an AS daughter. The frequencies with which w e detected mutations were 5 (14%) of 35 in sporadic cases and 8 (80%) of 10 in familial cases.