Background - The CFTR 5T variant, aka IVS8(5T) is not well understood, but it is getting increasing attention. It is carried by up to 10% of the U.S. population (yes, 10%), and, especially when found in trans to a major CF mutation, and when associated with a higher TG repeat sequence (e.g., TG12 or TG13), appears to contribute to a range of phenotypes, from CBAVD to sinusitis to full-blown CF. To some (e.g., Europe), the 5T (associated with (TG)13) is "CF-Causing"; to others, its effects are less certain.

The issue(s) - Because it is so common, and increasingly prevalent in newborn screening, there will be more and more patients identified with the 5T and with an "uncertain" prognosis. Sweat tests are often borderline, penetrance can be minimal or significant, organ-specific, or delayed over time. Those affected by the 5T could benefit greatly from a comprehensive analysis of known and likely outcomes in patients with the TG/13-5T/M and TG/12-5T/M genotype. Given the range of symptoms potentially attributable to the 5T, and its prevalence in the population, the opportunities for better understanding are promising. The fact that Ivacaftor may be an effective potentiator of the 5T's residual CFTR makes things all the more interesting...

Call to action - We have several hundred papers available on the subject. To get started, here's one paper to look at, and here's a simple spreadsheet, both with assumptions that could certainly be refined. If this project is up your alley, contact us, as we are eager to help you get going. Depending on your potential scope, we could double our grant offering to $10,000.