Three common CFTR mutations should be included in a neonatal screening programme for cystic fibrosis in Sweden

Children with cystic fibrosis (CF) diagnosed by neonatal screening have a b etter nutritional development and other advantages compared with those in a nonscreened group. The two-tier immunoreactive trypsinogen (IRT)/DNA scree ning protocol has been found superior to the single-tier IRT approach, impr oving the positive predictive value and thus reducing the false-positive ra te. However, variations of the DNA test are required for different populati ons. In this study we examined CFTR (cystic fibrosis transmembrane conducta nce regulator) mutations in 331 CF patients attending the centres in Stockh olm, Lund and Uppsala, comprising about 75% of the CF population in Sweden. The frequency of Delta F508 among CF alleles was 68.3% There were two othe r mutations, 394delTT and 3659delC, found to be fairly frequent, amounting to 8.5 and 7.9%, respectively. Other mutations were comparatively rare. A s imple and effective method of analysing the three mutations from Guthrie ca rds has been developed. Assuming Hardy-Weinberg equilibrium, 90% of our CF patients will be expected to carry at least one Delta F508 allele and 97.6% to carry at least one Delta F508, 394delTT or 3659delC copy. Including the latter two in a screening programme would thus substantially reduce the ri sk of a false-negative outcome.