The utility of the traditional medical genetics diagnostic evaluation in the context of next-generation sequencing for undiagnosed genetic disorders
The utility of the traditional medical genetics diagnostic evaluation in the context of next-generation sequencing for undiagnosed genetic disorders
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DOI：
10.1038/gim.2013.99
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发表时间：
2014-02-01
影响因子：
8.8
通讯作者：
Goldstein, David B.
中科院分区：
文献类型：
--
作者：
Shashi, Vandana;McConkie-Rosell, Allyn;Goldstein, David B.
目的：本研究的目的是评估传统的综合临床评估和靶向基因检测在普通遗传学诊所的诊断效果。这些数据对于开发临床和经济基础的诊断算法至关重要，这些算法考虑了呈现表型，传统遗传学检测以及下一代测序（全外显子组/基因组测序）的新兴作用。方法：我们回顾性分析了在三级医疗中心接受传统遗传诊断评估的500名未选择的连续患者的队列。我们计算了诊断率、就诊次数、基因检测和检测费用。结果：39例患者被确定为无遗传疾病；其余461人中有212人（46%）接受了基因诊断，其中72%在第一次就诊时被诊断出来。随后每次成功的遗传诊断的费用估计为25 000美元。结论：近一半的患者采用传统方法诊断，大多数在初次就诊时诊断。对于那些尚未确诊的患者，下一代测序可能在临床上和经济上都是有益的。估计下一代测序在未诊断的遗传疾病中的成功率为50%，在首次临床就诊后应用该技术可以提高遗传诊断率，并且每次成功诊断可节省相当大的成本。
Purpose: The purpose of this study was to assess the diagnostic yield of the traditional, comprehensive clinical evaluation and targeted genetic testing, within a general genetics clinic. These data are critically needed to develop clinically and economically grounded diagnostic algorithms that consider presenting phenotype, traditional genetics testing, and the emerging role of next-generation sequencing (whole-exome/genome sequencing).Methods: We retrospectively analyzed a cohort of 500 unselected consecutive patients who received traditional genetic diagnostic evaluations at a tertiary medical center. We calculated the diagnosis rate, number of visits to diagnosis, genetic tests, and the cost of testing.Results: Thirty-nine patients were determined to not have a genetic disorder; 212 of the remaining 461 (46%) received a genetic diagnosis, and 72% of these were diagnosed on the first visit. The cost per subsequent successful genetic diagnosis was estimated at $ 25,000.Conclusion: Almost half of the patients were diagnosed using the traditional approach, most at the initial visit. For those remaining undiagnosed, next-generation sequencing may be clinically and economically beneficial. Estimating a 50% success rate for next-generation sequencing in undiagnosed genetic disorders, its application after the first clinical visit could result in a higher rate of genetic diagnosis at a considerable cost savings per successful diagnosis.