*2.1.1. Screening techniques (Step 1)*

These approaches consist of genotyping a panel of frequent CF mutations using commercial kits (Table 1) that classically cover more than 80% of CF known mutations in European populations. Additional search for mutations specific to certain regions or ethnicities (fre‐ quency higher than 1% of CF alleles in the targeted population) completes the analyses.

Data on disease and carrier frequencies or mutation frequencies in various populations are available in the WHO report [8] and should be accurately known and used by laboratories.

For many patients carrying CF-causing mutations included in commercial panels, *CFTR* molecular analysis generally stops at this step. There is no need for additional studies, except the confirmation of mutations by a second method, as recommended by international guide‐ lines for genetics diagnosis.

### *2.1.2. Scanning techniques (Step 2)*

The high heterogeneity of *CFTR* mutations in CF and CFTR-RD populations makes the complete molecular screening of the 27 exons and parts of the regulatory regions (5'UTR, 3'UTR and partial intronic regions) essential.

Therefore, the analysis of the *CFTR* locus can be performed as follows:


These robust methods allow the detection of more than 97% of *CFTR* mutations involved in CF.
