CYSTIC FIBROSIS SCREENING: AN ALTERNATIVE PARADIGM

囊性纤维化（CF）是最常见的，致命的，常染色体隐性遗传 在美国白人中发现的一种疾病，影响约1/2500 出生 受影响的个体具有多效作用， 胰腺和胃肠道问题，可以有显着的临床 可变性直到最近，检测CF载体状态是不可能的 在受影响的孩子或亲属出生之前。 最近发现的 CF基因和检测CF等位基因的新方法的发展， 重新点燃了对CF的基于人群的携带者筛查的兴趣。 然而 CF潜在的等位基因异质性提出了一个问题， 被发现对测试的所有等位基因呈阴性的个体或夫妇可 仍然是其他未定义突变的携带者， 导致CF。 因此，筛选CF携带者存在以下问题： 潜在的接收者理解固有的概率信息 这将导致，2）如何最好地传达这些信息，3）在哪里 （4）测试对象;（5） 人们真的想知道他们是否是CF携带者吗？ 目前的模式为携带者筛选涉及遗传咨询师 提供非指导性信息，以便被咨询者能够了解 关于筛选的决定。 测试后，咨询继续 确保咨询者了解结果及其 暗示因为美国所有的遗传咨询师都不能提供 这项服务的潜在数量的高加索CF运营商，我们建议 来测试一种新的模式 我们的建议的两个主要目标是1） 确定一个道德上可接受的CF筛选程序的可行性 最大限度地减少个人咨询接触， 为那些筛查测试阴性的人提供测试，并提供个人 咨询主要针对筛查结果呈阳性的人，2） 确定的可接受性，准确性和经济效益， 用于携带者CF测试的自我管理手指针刺取样方法， 一般大众都能很方便地获得。 如果成功， 一种方法为社会提供了巨大的潜在利益，包括更好地 了解CF筛选的最佳方法并提高其产量 和准确性，同时降低相关的咨询和实验室成本。 这些见解将对许多潜在的应用产生影响 用于筛查可能在近期出现的家族性疾病， 未来

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.