Deciphering variants of unknown significance in Niemann Pick Type C
Awardee: Evgueni Ivakine
Institution: Hospital for Sick Children
Award Amount: $47,630
Funding Period: February 1, 2021 - January 31, 2022
Summary:
As we enter an age where we understand more about genetic disease, we are beginning to regularly implement genome sequencing and personalized medicine in clinical practice. These efforts are hampered by a lack of knowledge about how mutations contribute to disease. This is particularly the case for diseases like Niemann-Pick disease type C (NPC), a rare genetic disease in which most patients present with a mutation that has not previously been reported. This leads to lengthy wait times between presentation and definitive diagnosis, as specialized laboratories are required to biochemically diagnose each potential patient. Through our work, we aim demonstrate a new method to quickly and easily create every possible mutation in each DNA base in a critical region of the the NPC1 gene using next-generation CRISPR-based gene editing technologies. Once we have generated a group of these mutant cells, we will perform a functional test to rapidly ascertain if each would likely lead to developing the disease or not. After identifying disease-causing mutations, we will apply a drug, currently undergoing clinical trials for NPC, to further classify the disease-causing mutations as responders or non-responders to this treatment.