title: Detection of a deletion of exons 8-16 of the UBE3A gene in familial Angelman syndrome using a semi-quantitative dosage PCR based assay.
abstract: Angelman syndrome (AS) is a neurodevelopmental disorder caused by failure of expression of the maternal copy of the imprinted UBE3A gene through a variety of mechanisms detected by methylation studies, mutation analysis of UBE3A and FISH. In 10-15% of suspected cases of AS these investigations do not reveal a genetic abnormality. We report here the development of a semi-quantitative dosage PCR technique used to identify sub-microscopic deletions involving UBE3A. Using this method we analysed a panel of 26 patients from 24 families, all fulfilling the clinical criteria for AS. We identified a deletion of UBE3A exons 8-16 in a sibling pair. Analysis of parental samples revealed the same deletion in their phenotypically normal mother. This is an inexpensive and valuable method for detecting UBE3A deletions in a small but important proportion of AS cases of unidentifiable cause.
authors.affiliation: Academic Department of Medical Genetics, Saint-Mary's Hospital, Hathersage Road, Manchester, UK. Lauraannboyes@hotmail.com
authors.forename: L
authors.initials: L
authors.lastname: Boyes
authors.forename: A J
authors.initials: AJ
authors.lastname: Wallace
authors.forename: M
authors.initials: M
authors.lastname: Krajewska-Walasek
authors.forename: K H
authors.initials: KH
authors.lastname: Chrzanowska
authors.forename: J
authors.initials: J
authors.lastname: Clayton-Smith
authors.forename: S
authors.initials: S
authors.lastname: Ramsden
mesh_terms: D000293:Adolescent; D017204:Angelman Syndrome / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D017931:DNA Primers / Q000235:genetics; D005091:Exons; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D017931:DNA Primers; C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases