APPTT
PTAC/CFTR
CLIN
Rebecca Darrah, MS, PhD
Case Western Reserve University
Philip Farrell, MD, PhD
Departments of Pediatrics and Population Health Sciences, University of Wisconsin School of Medicine and Public Health
This symposium will explore the current data surrounding the wide range of CFTR expression/function and how it relates to phenotypic expression. It has long been postulated that there is some type of threshold of CFTR function that correlates with the emergence of clinical signs and symptoms, however the exact level of expression and/or function that represents this level is difficult to determine, likely varies with individual tissue types, and with environmental or external factors. Here we will explore these thresholds by exploring data from CFTR restoration using modulator therapy and other inventions. Additionally, we will use data from partial function variants observed in individuals with CRMS/CFSPID to determine whether inferences can be made about relationships between amount of CFTR function and clinical phenotypes in this setting. We will also explore how external changes in CFTR expression/function such as that resulting from cigarette exposure correlate with presentation of CF-like symptoms in individuals with COPD. Finally, a discussion on whether there is evidence for a heterozygote advantage in CF may help explain the relatively high frequency of CF carriers observed in many populations.