CYSTIC FIBROSIS SCREENING: AN ALTERNATIVE PARADIGM

囊性纤维化是最常见的致死性常染色体隐性遗传病 在美国高加索人中发现的疾病，大约每2500人中就有1人感染 出生。受影响的个体具有多效性，导致肺部、 胰腺和胃肠道问题，可能会有明显的临床症状 可变性。直到最近，还不可能检测到CF携带者状态 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 重新燃起了对基于人群的CF携带者筛查的兴趣。然而， Cf背后的等位基因异质性带来了这样的问题 所有被检测的等位基因均为阴性的个人或夫妇可 仍然是其他未定义突变的一个或多个携带者 导致CF. 因此，对CF承运人的筛查存在以下问题：1)可以 潜在的接收者理解固有的概率信息 这将导致，2)如何最好地传达该信息，3)在哪里 应该进行测试吗，4)应该为谁进行测试，5)应该为谁进行测试 有些人真的想知道自己是不是慢性萎缩性胃炎携带者？ 目前的携带者筛查模式包括遗传咨询师 提供非指导性信息，以便咨询公司能够 关于接受筛查的决定。测试后，咨询继续进行 确保咨询人员了解结果和他们的 言下之意。因为美国所有的遗传咨询师都无法提供 这项服务对潜在数量的高加索人CF携带者，我们建议 来测试一种新的范式。我们建议的两个主要目标是1) 确定伦理上可接受的慢性阻塞性肺疾病筛查计划的可行性 它最大限度地减少了个人咨询接触，结合了事前和事后 对筛查结果为阴性的人进行检测，并提供个人 咨询主要针对筛查呈阳性的人和2) 确定可接受性、准确性和经济效益 一种用于载体CF检测的自给指棒抽样方法， 可以方便地向普通民众提供。如果成功，这样的 一种方法为社会提供了巨大的潜在好处，包括更好的 对毛纤维最佳筛选方法的认识与提高得率 和准确性，同时减少相关的咨询和实验室成本。 这些见解将对许多潜在的应用程序产生影响 筛查近期可能出现的家族性疾病 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.