Studies to Determine How Angelman Syndrome-associated Missense Mutations Disrupt UBE3A Function
$200,000 (2 years)
Angelman syndrome (AS) is typically caused by genomic deletions that encompass the maternal copy of UBE3A. In some patients with AS, the UBE3A protein is present but with a single amino acid change known as a missense mutation. Investigators noticed that essentially all of the AS-associated missense mutations are located in specific regions (or “hot-spots”) of the UBE3A protein that are critical for UBE3A function. This research will evaluate how each known mutation affects UBE3A function. Furthermore, it has the potential to more accurately predict whether new mutations in UBE3A are benign or cause AS. Such studies could lead to therapeutics that stabilize UBE3A in a subset of patients with AS.
This study identified a pathway to regulate the activity of the UBE3A enzyme. The discovery has implications not only for Angelman syndrome, but dup15q syndrome and autism. The results were published in Cell.