Mutation Update for UBE3A Variants in Angelman Syndrome

作者：Sadikovic Bekim; Fernandes Priscilla; Zhang Victor Wei; Ward Patricia A; Miloslavskaya Irene; Rhead William; Rosenbaum Richard; Gin Robert; Roa Benjamin; Fang Ping^*

来源：Human Mutation, 2014, 35(12): 1407-1417.

DOI：10.1002/humu.22687

• UBE3A
• Angelman syndrome
• DNA sequencing
• genetic testing

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.

• 出版日期2014-12