title: Mutation Update for UBE3A variants in Angelman syndrome.
abstract: Angelman syndrome is a neurodevelopmental disorder caused by a deficiency of the imprinted and maternally expressed UBE3A gene. Although de novo genetic and epigenetic imprinting defects of UBE3A genomic locus account for majority of Angelman diagnoses, approximately 10% of individuals affected with Angelman syndrome are a result of UBE3A loss-of-function mutations occurring on the expressed maternal chromosome. The variants described in this manuscript represent the analysis of 2,515 patients referred for UBE3A gene sequencing at our institution, along with a comprehensive review of the UBE3A mutation literature. Of these, 267 (10.62%) patients had a report issued for detection of a UBE3A gene nucleotide variant, which in many cases involved family studies resulting in reclassification of variants of unknown clinical significance (VUS). Overall, 111 (4.41%) probands had a nucleotide change classified as pathogenic or strongly favored to be pathogenic, 29 (1.15%) had a VUS, and 126 (5.0%) had a nucleotide change classified as benign or strongly favored to be benign. All variants and their clinical interpretations are submitted to NCBI ClinVar, a freely accessible human variation and phenotype database.
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Bekim
authors.initials: B
authors.lastname: Sadikovic
authors.forename: Priscilla
authors.initials: P
authors.lastname: Fernandes
authors.forename: Victor Wei
authors.initials: VW
authors.lastname: Zhang
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Ward
authors.forename: Irene
authors.initials: I
authors.lastname: Miloslavskaya
authors.forename: William
authors.initials: W
authors.lastname: Rhead
authors.forename: Richard
authors.initials: R
authors.lastname: Rosenbaum
authors.forename: Robert
authors.initials: R
authors.lastname: Gin
authors.forename: Benjamin
authors.initials: B
authors.lastname: Roa
authors.forename: Ping
authors.initials: P
authors.lastname: Fang
mesh_terms: D017204:Angelman Syndrome / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases
keywords: Angelman syndrome; DNA sequencing; UBE3A; genetic testing