Table 2.
Classes of CFTR mutations, risk of EPI and therapeutic approach (adapted from CFTR2—Clinical and Functional Translational of CFTR and McKay et al.) [4,87].
| Class | Type of Defect | Risk of EPI | Examples of CFTR Mutations | Therapeutic Approach | Available Drugs |
|---|---|---|---|---|---|
| I | protein synthesis defect | 98% 99% 97% |
G542x W1282x R553x |
Genetic therapies Read-through agents |
— |
| II | protein trafficking | 98% 98% |
F508del N1303K |
Corrector (and potentiator) | Elexacaftor/tezacaftor/ivacaftor Lumacaftor/ivacaftor Tezacaftor/ivacaftor |
| III | gatting defect | 100% 96% 33% |
G970R G551D G551S |
Potentiator | Ivacaftor |
| IV | conductance defect | 0% 40% 68% |
G314E R334W R347P |
Potentiator | Ivacaftor |
| V | reduced protein synthesis | 43% 33% 29% |
2789 + 5G → A 3849 + 10KbC → T 3272-26A → G |
Amplifier | — |
| VI | decreased stability | — | c.120del123 rPhe580del |
Stabiliser | — |