Angelman Syndrome is primarily caused by which genomic event?

Angelman Syndrome is primarily caused by paternal imprinting, specifically the loss of function of the UBE3A gene, which is typically expressed from the maternal allele and silenced on the paternal allele in certain brain tissues due to genomic imprinting. In the context of Angelman Syndrome, the paternal allele is imprinted, meaning it is not expressed, which leads to the absence of the UBE3A protein and the resultant symptoms associated with the condition.

Paternal imprinting differs from other genomic events like maternal uniparental disomy (UPD), which refers to the inheritance of both alleles of a pair from the mother, or induced mutations, which are changes introduced to the DNA sequence through external factors. The characteristic features of Angelman Syndrome underscore the critical role of maternal expression and paternal silencing of the UBE3A gene, where the absence of maternal gene expression due to imprinting results in clinical manifestations. Understanding this mechanism highlights the importance of genomic parental origin in the pathogenesis of the syndrome.