As with all fields of medicine, the first step toward medical management of genetic disorders is obtaining an accurate diagnosis, which often requires testing at the molecular level. Unfortunately, given the large number of genetic conditions without a specific intervention, only rarely does a genetic diagnosis alter patient management-which raises the question, what is the added value of obtaining a molecular diagnosis? Given the fast-paced advancement of genomic technologies, this is an important question to address in the context of genome-scale testing. Here, we address the value of establishing a diagnosis using genome-scale testing and highlight the benefits and drawbacks of such testing. We also review and compare recent major studies implementing genome-scale sequencing methods to identify a molecular diagnosis in cohorts manifesting a broad range of Mendelian monogenic disorders. Finally, we discuss potential future applications of genomic sequencing, such as screening for rare conditions.

中文翻译：

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定义下一代测序时代的基因组诊断的临床价值。

与所有医学领域一样，遗传疾病医学管理的第一步是获得准确的诊断，这通常需要在分子水平上进行测试。不幸的是，鉴于大量的遗传疾病而没有特定的干预措施，遗传诊断很少改变患者的治疗方法，这提出了一个问题，获得分子诊断的附加价值是什么？鉴于基因组技术的飞速发展，这是在基因组规模测试中需要解决的重要问题。在这里，我们探讨了使用基因组规模测试建立诊断的价值，并强调了这种测试的利弊。我们还回顾并比较了最近的主要研究，这些研究实施了基因组规模的测序方法，以鉴定出表现出广泛的孟德尔单基因疾病的队列中的分子诊断。最后，我们讨论了基因组测序的潜在未来应用，例如罕见条件的筛选。