Newborn screening for cystic fibrosis in Wisconsin: first application of population-based molecular genetics testing.
Infants born in Wisconsin are being screened for cystic fibrosis (CF) associated with the F508 mutation. This screening program has been developed during 9 years of research supported by the National Institutes of Health and involves a unique, two-tier system employing measurement of immunoreactive trypsinogen (IRT) initially. When the IRT level is high, DNA is extracted from the neonatal dried blood specimen and analyzed for the F508 mutant allele, following polymerase chain reaction (PCR) amplification; the F508 mutation is present in more than 90% of CF patients and accounts for the common, severe form of the disease. Infants with a positive DNA test are either CF heterozygote carriers or CF patients, depending on the results of a sweat test, which should be performed at 4 weeks of age. Screening the newborn population for CF provides the opportunity for early nutritional and respiratory interventions, as well as genetic counseling. This represents the first population-based application of molecular genetics for detection of a major congenital disorder causing serious public health problems. The process by which the recommendation was reached to screen for CF is described in this article, along with new information on the pathogenesis of CF, its clinical presentation, the rationale for newborn screening, and the method developed for the screening program.