The Cystic Fibrosis Mutation Database currently has over 1,900 classified mutations that have been found in CFTR. However, the effect of most of these mutations remains unknown. To address this issue, the Clinical and Functional Translation of CFTR (CFTR2) project was started. The goal of CFTR2 is to determine if a given rare CFTR mutation causes cystic fibrosis, and if so, how severe. To accomplish this goal, CFTR2 uses clinical data from patients with a known mutation as well as the functional data on the processing of CFTR with that same mutation in vitro. Interestingly, there are a number of mutations where patients have a mild clinical phenotype despite the fact that the mutation results in poor processing or function of CFTR in vitro. My project is to assess these CFTR mutations to determine the cause of discrepancies between the clinical and in vitro data.
Experimental assessment of splicing variants using expression minigenes and comparison with in silico predictions. Sharma N, Sosnay PR, Ramalho AS, Douville C, Franca A, Gottschalk LB, Park J, Lee M, Vecchio-Pagan B, Raraigh KS, Amaral MD, Karchin R, Cutting GR. Hum Mutat. 2014 Oct;35(10):1249-59. Epub 2014 Sep 10. PMID:25066652