PCR-BASED SCREENING FOR CYSTIC-FIBROSIS CARRIER MUTATIONS IN AN ETHNICALLY DIVERSE PREGNANT POPULATION

As the most common lethal autosomal recessive disorder in North Americ a, cystic fibrosis (CF) is an obvious candidate for general population carrier screening. Although the identification of the causative gene has made detection of asymptomatic carriers possible, the extreme hete rogeneity of its mutations has limited the sensitivity of the availabl e DNA screening tests and has called into question their utility when they are applied to patients with no family history of the disease. Th e purpose of this study was to determine the technical feasibility, pa tient acceptance and understanding, and psychosocial impact of large-s cale CF carrier screening in an ethnically diverse pregnant population . A total of 4,739 pregnant women attending prenatal clinics located i n both an academic medical center and a large HMO were invited in pers on to participate. Of this group, 3,543 received CF instruction and as sessments of knowledge and mood, and 3,192 underwent DNA testing for t he six most common CF mutations, by means of a noninvasive PCR-based r everse-dot-blot method. Overall participation rates (ranging from 53% at the HMO to 77% at the academic center) and consent rates for DNA te sting after CF instruction (>98%) exceeded those of most other America n studies. The PCR-based screening method worked efficiently on large numbers of samples, and 55 carriers and one at-risk couple were identi fied. Understanding of residual risk, anxiety levels, and overall sati sfaction with the program were acceptable across all ethnic groups. Ou r strategy of approaching a motivated pregnant population in person wi th a rapid and noninvasive testing method may provide a practical mode l for developing a larger CF screening program targeting appropriate h igh-risk groups at the national level, and may also serve as a paradig m for population-based screening of other genetically heterogeneous di sorders in the future.