A three-year follow-up study evaluating clinical utility of exome sequencing and diagnostic potential of reanalysis
A three-year follow-up study evaluating clinical utility of exome sequencing and diagnostic potential of reanalysis
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DOI：
10.1038/s41525-020-00144-x
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发表时间：
2020-09-10
影响因子：
5.3
通讯作者：
Chung, Brian H. Y.
中科院分区：
文献类型：
--
作者：
Fung, Jasmine L. F.;Yu, Mullin H. C.;Chung, Brian H. Y.
外显子测序（ES）已成为临床遗传学中重要的诊断工具之一，据报道诊断率为25-58％。许多研究说明了ES的诊断和直接临床影响。但是，多达75％的个体仍未诊断，并且有稀缺的证据支持临床公用事业，超过1年的随访期。这是Mak等人对我们之前出版物的3年后续分析。 （NPJGenom。Med.3：19，2018），评估ES的长期临床实用性和外来重新分析的诊断潜力。初始研究的诊断产量为41％（43/104）。在46个未诊断的个体中，外来的重新分析已实现了12种新诊断。与初始分析相比，额外的收率至少为12％（从41％增加到至少53％）。经过3。4年的中位随访期后，在72.2％的个体（26/36）中观察到临床管理的变化，导致四个人（11％）的临床结果正变化。这四个人每年最低的医疗保健费用节省最低HKD $ 152,078（19,497美元； EURO17,282）。在此期间，共有五个家庭的六次怀孕。在四个怀孕中进行了产前诊断。一个胎儿受到影响并导致终止。没有父母接受植入前遗传诊断。这项为期三年的随访研究表明，ES在个人，家族和卫生系统水平上的长期临床实用性以及随后重新分析的有希望的诊断潜力。这突出了在临床环境中实施ES和定期重新分析的好处。
Exome sequencing (ES) has become one of the important diagnostic tools in clinical genetics with a reported diagnostic rate of 25-58%. Many studies have illustrated the diagnostic and immediate clinical impact of ES. However, up to 75% of individuals remain undiagnosed and there is scarce evidence supporting clinical utility beyond a follow-up period of >1 year. This is a 3-year follow-up analysis to our previous publication by Mak et al. (NPJ Genom. Med.3:19, 2018), to evaluate the long-term clinical utility of ES and the diagnostic potential of exome reanalysis. The diagnostic yield of the initial study was 41% (43/104). Exome reanalysis in 46 undiagnosed individuals has achieved 12 new diagnoses. The additional yield compared with the initial analysis was at least 12% (increased from 41% to at least 53%). After a median follow-up period of 3.4 years, change in clinical management was observed in 72.2% of the individuals (26/36), leading to positive change in clinical outcome in four individuals (11%). There was a minimum healthcare cost saving of HKD$152,078 (USD$19,497; euro17,282) annually for these four individuals. There were a total of six pregnancies from five families within the period. Prenatal diagnosis was performed in four pregnancies; one fetus was affected and resulted in termination. None of the parents underwent preimplantation genetic diagnosis. This 3-year follow-up study demonstrated the long-term clinical utility of ES at individual, familial and health system level, and the promising diagnostic potential of subsequent reanalysis. This highlights the benefits of implementing ES and regular reanalysis in the clinical setting.