Table 3.
(A) Disease phenotypes associated with CFTR mutation combinations not currently described in the literature. (B) Disease phenotypes for pwCF with CFTR mutation combinations reported to be ‘non-disease causing’ in the CFTR2 database.
| (A) Rare CFTR Mutation Combinations—Phenotypes | ||||||||||
| CFTR Genotype | Baseline FEV1 | BMI |
Sweat
Chloride (mmol/L) |
Pancreatic
Insufficiency |
CFRD | CFLD | HbA1c | Bone Health (BMD) | Microbiology | CFTR Modulator |
| P67L/3272-26A->G | 1.38 (52.1%) | 29.4 | 51 | Yes | No | No | 5.5% | Osteoporosis | PsA, S. aureus |
Tezacaftor/ivacaftor |
| W1282X/I1269N | 1.65 (52.2%) | 35.8 | N/A | Yes | No | No | 5.30% | Osteoporosis | PsA (intermittent) | Nil |
| F508del/V1108L (c.3322delG) | 3.75 (103.4%) | 21.8 | N/A | Yes | No * | No | 5.70% | Normal | PsA, S. aureus, Asp. fumigatus |
Elexacaftor/tezacaftor /ivacaftor |
| F508del/V1108L (c.3322delG) | 2.37 (68.5%) | 19.4 | N/A | Yes | Yes | Yes | 10.60% | Osteopenia | PsA, S. aureus, Asp. fumigatus |
Elexacaftor/tezacaftor /ivacaftor |
| G542X/T1246I | 1.25 (47.6%) | 24.3 | 53 | No | No | No | 5.80% | Normal | PsA | Nil |
| 1898+1G->A (1766+1G>A)/2622+1G->T (2490+1G>T) | 3.04 (95.0%) | 26.1 | N/A | Yes | Yes | No | 5.80% | Normal | PsA, S. aureus |
Nil |
| E60X/Q1291H | 0.95 (35.4%) | 28.6 | 49 | Yes | Yes | No | 8.50% | Osteopenia | PsA, S. aureus |
Nil |
| G551D/D110H | 2.61 (63.2%) | 24.7 | 28 | Yes | No | No | 5.30% | Osteopenia | Nil regular | Ivacaftor |
| G551D/D110H | 4.03 (104.4%) | 22.2 | 23 | Yes | No | No | 5.00% | Osteopenia | Nil regular | Ivacaftor |
| 1249-1G>A (c.1117-5A>G)/c.1210-34(TG)12(T)5 | 2.55 (54.5%) | 30.7 | 57 | No | No | No | N/A | No BMD | Nil regular | Nil |
| V520F/1461ins4 | 2.90 (67.6%) | 23.6 | N/A | Yes | No | No | 6.10% | Normal | S. aureus | Nil |
| (B) Non-disease Causing CFTR Mutation Combinations—Phenotypes | ||||||||||
| CFTR Genotype | Baseline FEV1 | BMI |
Sweat
Chloride (mmol/L) |
Pancreatic
Insufficiency |
CFRD | CFLD | HbA1c |
Bone Health
(BMD) |
Microbiology | CFTR Modulator |
| F508del/I148T | 2.79 (67.8%) | 20.9 | 110 | Yes | No * | No | 5.30% | Osteopenia | S. aureus | Elexacaftor/tezacaftor /ivacaftor |
| F508del/M470V | 0.94 (24.1%) | 34.3 | 43 | Yes | Yes | Yes | 9.00% | Osteopenia | PsA | Elexacaftor/tezacaftor /ivacaftor |
| F508del/I1027T | 1.49 (39.2%) | 26.4 | N/A | Yes | No | Yes | 5.00% | Normal | PsA | Elexacaftor/tezacaftor /ivacaftor |
OGTT—oral glucose tolerance test (* impaired glucose tolerance); CFRD—CF-related diabetes; CFLD—CF-related liver disease; BMD—bone mineral density scan; PsA—Pseudomonas aeruginosa; S. aureus—Staphylococcus aureus; Asp. fumigatu—Aspergillus fumigatus.