Mutation Update for UBE3A Variants in Angelman Syndrome. Issue 12 (December 2014)

• Record Type: Journal Article
• Authors: Sadikovic, Bekim; Fernandes, Priscilla; Zhang, Victor Wei; Ward, Patricia A.; Miloslavskaya, Irene; Rhead, William; Rosenbaum, Richard; Gin, Robert; Roa, Benjamin; Fang, Ping
• Is Part Of: Human mutation. Volume 35:Issue 12(2014:Dec.)
• Page Start: 1407
• Page End: 1417
• Publication Date: 2014-12
• Subjects: Human chromosome abnormalities -- Periodicals; Mutation (Biology) -- Periodicals; 616.04205
• DOI: 10.1002/humu.22687
• Languages: English
• ISSNs: 1059-7794

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p>Angelman syndrome is a neurodevelopmental disorder caused by a deficiency of the imprinted and maternally expressed <italic>UBE3A</italic> gene. Although de novo genetic and epigenetic imprinting defects of <italic>UBE3A</italic> 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 <italic>UBE3A</italic> gene sequencing at our institution, along with a comprehensive review of the <italic>UBE3A</italic> mutation literature. Of these, 267 (10.62%) patients had a report issued for detection of a <italic>UBE3A</italic> 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.</p> </abstract>