Background: Cystic fibrosis (CF) is caused by compound heterozygosity or homozygosity of CF transmembrane conductance regulator gene (CFTR) mutations. Phenotypic variability associated with certain mutations makes genetic counselling difficult, notably for R117H, whose disease phenotype varies from asymptomatic to classical CF. The high frequency of R117H observed in CF newborn screening has also introduced diagnostic dilemmas. The aim of this study was to evaluate the disease penetrance for R117H in order to improve clinical practice. Methods: The phenotypes in all individuals identified in France as compound heterozygous for R117H and F508del, the most frequent CF mutation, were described. F508del] was estimated at 0.03% and that of severe CF in adulthood at 0.06%. Conclusions: These results suggest that R117H should be withdrawn from CF mutation panels used for screening programmes. The real impact of so-called disease mutations should be assessed before including them in newborn or preconceptional carrier screening programmes.Cystic fibrosis (CF, MIM 219700) is one of the most frequent life shortening autosomal recessive diseases, characterised in its classical form by chronic pulmonary obstruction and infections, pancreatic insufficiency, male infertility and elevated sweat chloride concentrations.

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