CYSTIC FIBROSIS SCREENING: AN ALTERNATIVE PARADIGM

囊性纤维化（CF）是最常见的、致死性的常染色体隐性遗传病

Cystic Fibrosis (CF) is the most common, lethal, autosomal recessive disease seen in Caucasians in the U.S. affecting approximately 1 in 2500 births. Affected individuals have pleiotropic effects causing pulmonary, pancreatic and gastrointestinal problems that can have marked clinical variability. Until recently, detection of CF carrier status was impossible before the birth of an affected child or relative. The recent discovery of the CF gene and the development of new methods to detect CF alleles has rekindled interest in population based carrier screening for CF. However the allelic heterogeneity underlying CF presents the problem that individuals or couples found to be negative for all alleles tested may still be a carrier or carriers for other, undefined mutations that can cause CF. Thus screening for CF carriership presents the following problems: 1) can potential recipients understand the inherently probabilistic information that would result, 2) how is this information best conveyed, 3) where should testing be done, 4) for whom should testing be done and 5) do individuals actually want to know if they are CF carriers? The current paradigm for carrier screening involves a genetic counselor providing non-directive information so consultands can make informed decisions regarding being screened. After testing, counseling continues to ensure that the consultand understands both the results and their implication. Since all genetic counselors in the U.S. could not provide this service to the potential number of Caucasian CF carriers, we propose to test a new paradigm. The two major goals of our proposal are 1) determine the feasibility of an ethically acceptable CF screening program which minimizes personal counseling contact, incorporates prior and post testing for those with negative screening tests and provides personal counseling primarily for those with positive screening tests and 2) to determine the acceptability, accuracy and economic benefits of a self-administered fingerstick sampling method for carrier CF testing which is conveniently available to the general population. If successful, such an approach offers great potential benefit to society including better understanding of optimal methods of CF screening and improving its yield and accuracy while reducing the associated counseling and laboratory costs. These insights would have implications for the many potential applications for screening for familial disorders that are likely to arise in the near future.