Reducing diagnostic turnaround times of exome sequencing for families requiring timely diagnoses
Reducing diagnostic turnaround times of exome sequencing for families requiring timely diagnoses
复制标题
DOI：
10.1016/j.ejmg.2017.08.011
复制
发表时间：
2017-11-01
影响因子：
1.9
通讯作者：
Faivre, Laurence
中科院分区：
文献类型：
--
作者：
Bourchany, Aurelie;Thauvin-Robinet, Christel;Faivre, Laurence
背景和目的：全外显子组测序（WES）现已进入医疗实践，在罕见孟德尔疾病的诊断中具有强大的应用。虽然WES的实用性和成本效益已被广泛证明，但必须减少诊断周转时间，使WES成为一线程序。自2011年以来，实验室程序的自动化和测序化学的进步使得在50小时内进行诊断性全基因组测序成为可能，从血液样本到疑似遗传疾病的分子诊断。利用这些进步，这项研究的主要目的是提高周转时间为sequencingresults.Methods：WES提出了29例严重未确诊的疾病与发育异常，并面临着医疗情况需要快速诊断。每个家庭都同意了。提取的DNA在NextSeq 500（Illumina）仪器上测序。按照标准程序分析数据。使用内部软件解释变体。每个罕见的变异影响蛋白质序列与临床相关性进行了测试，为家庭segregation.Results：诊断率为45%（13/29），平均周转时间为40天，从收到的标本交付结果的参考医生。除了允许遗传咨询，阳性家庭的快速诊断导致两个产前诊断和两个列入临床tests.Conclusions：这项试点研究证明了快速诊断WES在我们的初级遗传学中心的可行性。它减少了诊断过程，并帮助为家庭提供支持。(C)2017 Elsevier Masson SAS。All rights reserved.
Background and objective: Whole-exome sequencing (WES) has now entered medical practice with powerful applications in the diagnosis of rare Mendelian disorders. Although the usefulness and cost-effectiveness of WES have been widely demonstrated, it is essential to reduce the diagnostic turnaround time to make WES a first-line procedure. Since 2011, the automation of laboratory procedures and advances in sequencing chemistry have made it possible to carry out diagnostic whole genome sequencing from the blood sample to molecular diagnosis of suspected genetic disorders within 50 h. Taking advantage of these advances, the main objective of the study was to improve turnaround times for sequencing results.Methods: WES was proposed to 29 patients with severe undiagnosed disorders with developmental abnormalities and faced with medical situations requiring rapid diagnosis. Each family gave consent. The extracted DNA was sequenced on a NextSeq500 (Illumina) instrument. Data were analyzed following standard procedures. Variants were interpreted using in-house software. Each rare variant affecting protein sequences with clinical relevance was tested for familial segregation.Results: The diagnostic rate was 45% (13/29), with a mean turnaround time of 40 days from reception of the specimen to delivery of results to the referring physician. Besides permitting genetic counseling, the rapid diagnosis for positive families led to two pre-natal diagnoses and two inclusions in clinical trials.Conclusions: This pilot study demonstrated the feasibility of rapid diagnostic WES in our primary genetics center. It reduced the diagnostic odyssey and helped provide support to families. (C) 2017 Elsevier Masson SAS. All rights reserved.