Presenting Diagnostic Results from Large-Scale Clinical Mutation Testing

描述（由申请人提供）：随着基因分型方法的最新进展，特别是DNA微阵列和芯片扫描仪器的改进，现在可以在技术上和经济上对大量患者进行数千种与孟德尔病表型相关的已知突变的测试。这种可能性提示了大规模突变阵列在分子诊断和遗传风险评估中的许多临床应用，例如产前检测导致严重遗传疾病的最常见突变，筛查常染色体隐性或x连锁突变，以及对一系列成人发病疾病的预测性检测。然而，如果要将大规模突变检测有效地整合到临床护理中，必须首先解决几个重大的伦理问题。大规模的突变检测将产生大量的诊断信息。考虑到检测到的大量突变，不可能像在更传统的基因检测程序中所做的那样，就大规模突变阵列的每个单独组成部分的技术特征（如假阳性和假阴性率）向患者提供咨询。也不可能就具体的医疗干预措施或在检测前确定数千种可能突变的确证性诊断测试向患者提供建议，而在建议进行基因检测的其他情况下，通常会这样做。由于大规模突变检测将需要偏离这些和其他临床遗传学的专业标准，因此以审慎的方式引入这种新形式的基因检测是至关重要的，这种方式应考虑到患者和遗传专业人员的期望、需求和价值观。这项研究将检查患者和专业人士对大规模临床突变检测诊断结果的理解。其目的是：(1)描述患者和基因专业人员对于在进行大规模临床突变检测之前应该与患者讨论的诊断可能性类型的态度和信念，以及(2)描述患者和基因专业人员对于在进行大规模临床突变检测后应该返回的诊断结果类型的态度和信念。这些实证结果将用于制定关于大规模临床突变检测诊断结果呈现的实用建议。关于患者和专业人员对这种新形式基因检测的理解的系统数据至关重要，因为这些数据将为遗传咨询实践、关于返回诊断结果的决定以及在患者护理中适当使用大规模突变检测的判断提供信息。本研究将检查患者和专业人员对大规模突变检测诊断结果的态度和信念。关于患者和专业人员对这种新形式基因检测的理解的系统数据至关重要，因为这些数据将为遗传咨询实践、关于返回诊断结果的决定以及关于将新的基因组技术引入患者护理的判断提供信息。

DESCRIPTION (provided by applicant): With recent advances in genotyping methods, specifically improvements in DNA microarrays and chip- scanning instrumentation, it is now technically possible and economically feasible to test large numbers of patients for several thousand known mutations associated with Mendelian disease phenotypes. This possibility suggests numerous clinical applications of large-scale mutation arrays in molecular diagnosis and genetic risk assessment, such as prenatal testing for the most common mutations responsible for severe genetic disorders, screening for autosomal recessive or X-linked mutations, and predictive testing for a range of adult-onset disorders. If large-scale mutation testing is to be integrated effectively into clinical care, however, several significant ethical issues must first be addressed. Large-scale mutation testing will generate an enormous amount of diagnostic information. Given the large number of mutations examined, it will not be possible to counsel patients on technical features of each individual component of a large-scale mutation array, such as false-positive and false-negative rates, as would be done in more traditional genetic testing procedures. Nor will it be possible to advise patients on specific medical interventions or confirmatory diagnostic tests associated with identifying each of several thousand possible mutations prior to testing, as frequently would be done in other situations in which genetic testing is recommended. Since large-scale mutation testing will require a departure from these and other professional standards in clinical genetics, it is vitally important that this new form of genetic testing be introduced in a deliberative manner that is informed by the expectations, needs, and values of both patients and genetic professionals. This research study will examine patient and professional understandings of diagnostic results from large-scale clinical mutation testing. Its aims are to: (1) describe the attitudes and beliefs of patients and genetic professionals regarding the types of diagnostic possibilities that should be discussed with patients prior to large-scale clinical mutation testing, and (2) characterize the attitudes and beliefs of patients and genetic professionals regarding the types of diagnostic results that should be returned following large-scale clinical mutation testing. These empirical results will be used to develop practical recommendations regarding the presentation of diagnostic results from large-scale clinical mutation testing. Systematic data on patients' and professionals' understandings of this new form of genetic testing are critically important, as these data will inform genetic-counseling practices, decisions about the return of diagnostic results, and judgments about the appropriate use of large-scale mutation testing in patient care. Narrative This research study will examine patients' and professionals' attitudes and beliefs regarding the presentation of diagnostic results from large-scale mutation testing. Systematic data on patient and professional understandings of this new form of genetic testing are critically important, as these data will inform genetic-counseling practices, decisions about the return of diagnostic results, and judgments about the introduction of new genomic technologies into patient care.