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

• Published in: American journal of medical genetics. Part A Vol. 126A; no. 3; pp. 248 - 252
• Main Authors: Rapakko, Katrin, Kokkonen, Hannaleena, Leisti, Jaakko
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 30.04.2004
• Subjects: Adult; Angelman syndrome; Angelman Syndrome - genetics; Case-Control Studies; Child; Child, Preschool; Chromosomes, Human, Pair 15 - genetics; CSGE; DNA Mutational Analysis; Electrophoresis - methods; Female; Finland; Humans; Male; Mutation; Nucleic Acid Conformation; Pedigree; Polymorphism, Single-Stranded Conformational; somatic mosaicism; UBE3A mutations; Ubiquitin-Protein Ligases - genetics
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.20587

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. © 2003 Wiley‐Liss, Inc.