title: UBE3A gene mutations in Finnish Angelman syndrome patients detected by conformation sensitive gel electrophoresis.
abstract: 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.
authors.affiliation: Department of Clinical Genetics, Oulu University Hospital, University of Oulu, Oulu, Finland.
authors.forename: Katrin
authors.initials: K
authors.lastname: Rapakko
authors.forename: Hannaleena
authors.initials: H
authors.lastname: Kokkonen
authors.forename: Jaakko
authors.initials: J
authors.lastname: Leisti
mesh_terms: D000328:Adult; D017204:Angelman Syndrome / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D004252:DNA Mutational Analysis; D004586:Electrophoresis / Q000379:methods; D005260:Female; D005387:Finland; D006801:Humans; D008297:Male; D009154:Mutation; D009690:Nucleic Acid Conformation; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases