NEONATAL SCREENING FOR CYSTIC-FIBROSIS - RESULT OF A PILOT-STUDY USING BOTH IMMUNOREACTIVE TRYPSINOGEN AND CYSTIC-FIBROSIS GENE MUTATION ANALYSES

We have evaluated a two-tier neonatal cystic fibrosis (CF) screening o f immunoreactive trypsinogen (IRT) followed by CFTR gene mutation anal ysis using a systematic scanning of exons 7, 10, and 11, and, if neces sary, by direct DNA sequencing. Over an 18-month period we screened 32 ,300 neonates born in the western part of Britanny. The first tier, in volving IRT screening at 3 days of age, utilizes a low elevation of th e trypsinogen level (600 ng/ml), which is highly sensitive. The second tier, which corresponds to the exhaustive screening for mutations in three exons of the gene, is highly specific for this population (Brita nny). The false positive rate is very low. and no false negatives have been reported to date. This strategy has allowed the identification o f five novel alleles (V322A, V317A, 1806 del A, R553G, G544S). Moreove r the test can be adapted to other countries in which the distribution of mutations is established.