Presenting Diagnostic Results from Large-Scale Clinical Mutation Testing

描述(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，现在检测大量患者与孟德尔病表型相关的数千个已知突变在技术上和经济上都是可行的。这种可能性暗示了大规模突变阵列在分子诊断和遗传风险评估中的大量临床应用，例如对导致严重遗传疾病的最常见突变的产前检测，对常染色体隐性突变或X连锁突变的筛选，以及对一系列成人发病疾病的预测测试。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要的伦理问题。大规模的突变检测将产生大量的诊断信息。鉴于检查的突变数量众多，不可能像在更传统的基因检测程序中那样，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。在检测之前，也不可能就与识别数千个可能的突变中的每一个相关的特定医疗干预或验证性诊断测试向患者提供建议，而在其他建议进行基因检测的情况下，通常会这样做。由于大规模突变检测将要求偏离临床遗传学中的这些和其他专业标准，因此以慎重的方式引入这种新的基因检测形式至关重要，这种新形式的基因检测以患者和基因专业人员的期望、需求和价值观为依据。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。它的目的是：(1)描述患者和遗传专业人员对在大规模临床突变检测之前应与患者讨论的诊断可能性类型的态度和信念，以及(2)描述患者和遗传专业人员对大规模临床突变检测后应返回的诊断结果类型的态度和信念。这些经验结果将被用来制定关于呈现大规模临床突变测试的诊断结果的实用建议。关于患者和专业人员对这种新形式的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策以及关于在患者护理中适当使用大规模突变检测的判断提供信息。这项研究将考察患者和专业人员对呈现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的基因测试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.