Cystic Fibrosis, CFTR Gene
Definition
An inherited disease characterized by thickened secretions due to a defect in the CFTR (cystic fibrosis transmembrane conductance regulator) gene; it affects the lungs, the pancreas and other organs.
Most common variant: p.Phe508del (F508del, c.1521_1523delCTT), the most common pathogenic variant in individuals of Northern European origin and a founder variant in many populations.
Diagnosis, two routes are used together:
| Method | Threshold / Criterion |
|---|---|
| Sweat chloride test (gold standard) | ≥60 mmol/L → diagnostic, independently of the molecular result |
| 30 to 59 mmol/L (intermediate value) → requires specialist evaluation | |
| Molecular testing | Detection of biallelic pathogenic variants in CFTR |
| Nasal potential difference | Alternative method |
Important: The sweat test can establish the diagnosis independently of genetic confirmation. In other words, if the sweat chloride is ≥60 mmol/L, the diagnosis is valid even if no variant is found on genetic testing. This is related to the fact that more than 2,000 variants exist in CFTR and panels cannot cover all of them.
Inheritance
Autosomal recessive
Risks and Limitations
Carrier screening panels generally cover the most common variants; rare variants can be missed. A negative result reduces the risk but does not eliminate it (residual risk).