Genotype-phenotype relationship for five CFTR mutations frequently identified in western France

Cystic fibrosis (CF) is the most common inherited disorder in Caucasian populations, with more than 1000 cystic fibrosis transmembrane conductance regulator (CFTR) mutations presently described. The distribution of the mutations ranges widely between countries and/or ethnic groups. Multicentric studies are usually needed to study the genotype-phenotype correlations.

Since 1992, the French CF Registry (FCFR) has collected and analyzed data from most of the CF patients regularly seen in CF care centres in France. We compared the mutation distribution of the patients born in western France to that of those born elsewhere in France. Then we extracted the available data for all the compound heterozygotes carrying the DeltaF508 allele and one of the following mutations: DeltaI507, 1078delT, 4005+1G->A, E60X and W846X, and matched a patient homozygous for the DeltaF508 mutation for each of them.

Western France appeared to have a specific distribution of some CF mutations. Furthermore, disparities were found regarding the mutation repartition (DeltaI507 in Normandy, 1078delT, 4005+1G->A and W846X in western Brittany). Genotype-phenotype correlations showed a wide heterogeneity. Although variations were found, DeltaI507/DeltaF508, 4005+1G->A/DeltaF508 and 1078delT/DeltaF508 patients appeared to have a similar disease as the DeltaF508/DeltaF508 patients. Although the W846X and E60X mutations should be considered as severe alleles as regards to pancreatic function, they were associated with less severe pulmonary manifestations and, probably, better prognosis.

The knowledge of the distribution of uncommon CF mutations specific to particular areas and of their associated phenotype makes up an essential tool in the management of local CF patients.