Excessive UBE3A dosage impairs fine-tuning of retinoid acid signaling in autism spectrum disorders

The autism spectrum disorders (ASD) are a collection of disorders with heterogeneous etiology, exhibiting common traits including impaired social interactions and communications, repetitive behaviors. 15q11-q13 copy number variations (CNV) were found in 1-3% of ASD cases; of which the detailed mechanism of the major contributor UBE3A gene acted still remained elusive. Here we identified a key enzyme in RA synthesis, negatively regulated in ubiquitination-dependent mode promoted by UBE3A. Our data provide evidences linking UBE3A hyperactivity with ASD phenotypes, with implications for understanding ASD etiology and providing potential interventions in ASD clinical therapy. To identify whether CNV variations existed within different patients diagnosed with ASD, genomic DNA were extracted from three patient blood samples and investigated using Human660W-Quad Beadchip assay.