Figure 2.

Molecular diagnostics for Angelman syndrome (AS). For those suspected with AS clinically, methylation analysis of the chromosome 15q11–13 region can be performed using methylation-sensitive multiplex ligation-dependent probe amplification (MS-MLPA). For those with normal methylation results, UBE3A gene sequencing is recommended to detect the UBE3A gene mutation. If UBE3A gene mutation is not detected, AS is excluded, and other diseases should be considered. For those with abnormal methylation results and deletion detected, AS due to del15q11–13 is diagnosed; for those without deletion, microsatellite linkage analysis can be done to differentiate paternal uniparental disomy (UPD) or imprinting defects.