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Newborn screening for cystic fibrosis in Wisconsin: first application of population-based molecular genetics testing
P M Farrell1, R A Aronson, G Hoffman
1Department of Health and Social Services, University of Wisconsin, Madison 53792-4108.
Insights
Wisconsin newborns are screened for cystic fibrosis (CF) using a two-tier system. Early detection via immunoreactive trypsinogen (IRT) and DNA testing allows for timely interventions and genetic counseling for this serious congenital disorder.
Area of Science:
- Biochemistry
- Genetics
- Public Health
Background:
- Cystic Fibrosis (CF) is a major congenital disorder with serious public health implications.
- The F508 mutation accounts for over 90% of severe CF cases.
- Newborn screening for CF enables early diagnosis and management.
Purpose of the Study:
- To describe the development and implementation of a population-based newborn screening program for Cystic Fibrosis in Wisconsin.
- To detail the two-tier screening methodology involving immunoreactive trypsinogen (IRT) and DNA analysis for the F508 mutation.
- To highlight the public health benefits of early CF detection through newborn screening.
Main Methods:
- A nine-year research effort supported by the National Institutes of Health led to a two-tier screening protocol.
- Initial screening involves measuring immunoreactive trypsinogen (IRT) levels in neonatal dried blood specimens.
- High IRT levels trigger DNA analysis for the F508 mutant allele using polymerase chain reaction (PCR) amplification.
Main Results:
- The F508 mutation is present in over 90% of CF patients, representing the most common and severe form of the disease.
- Infants with positive DNA tests require sweat tests at 4 weeks to differentiate between CF patients and heterozygote carriers.
- This program represents the first population-based application of molecular genetics for detecting a major congenital disorder.
Conclusions:
- Newborn screening for CF offers opportunities for early nutritional and respiratory interventions.
- Genetic counseling is a crucial component of the newborn screening program.
- Early detection and intervention through this molecular genetics-based screening program can significantly improve outcomes for infants with CF.
Abstract:
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.