UBE3A gene mutations in Finnish Angelman syndrome patients detected by conformation sensitive gel electrophoresis.

Angelman syndrome (AS) is a neurogenetic disorder associated with a loss of maternal gene expression in chromosome region 15q11-q13 due to either maternal deletion, paternal uniparental disomy (UPD), imprinting mutation, or mutation in the UBE3A gene. UBE3A encodes an ubiquitin-protein ligase and shows brain-specific imprinting. We have done conformation sensitive gel electrophoresis (CSGE) mutation analysis of the UBE3A coding region in nine AS patients, who had shown a normal biparental inheritance and methylation pattern of the 15q11-q13. Disease-causing mutations were identified in five of them: three deletions (1930delAG, 3093delAAGA) and two missense mutations (902A --> C, 975T --> C). Both deletions have also been detected in other AS patients, suggesting these sites may be prone to deletions in the UBE3A gene. All AS cases were sporadic, but a mosaicism for mutation 902A --> C was present in a patient's mother. Screening for the UBE3A mutations in the AS patients was found useful both for the confirmation of diagnosis and genetic counseling. CSGE was found to be a sensitive and simple screening method for these mutations.