Reference Center for Inborn Errors of Metabolism (ORPHA67872), University Hospital of Nancy, 54000, Nancy, France.
Department of Pediatrics, University Hospital of Nancy, 54000, Nancy, France.
Hum Genet. 2022 Jul;141(7):1269-1278. doi: 10.1007/s00439-021-02358-0. Epub 2021 Sep 8.
The emergence of next-generation sequencing enabled a cost-effective and straightforward diagnostic approach to genetic disorders using clinical exome sequencing (CES) panels. We performed a retrospective observational study to assess the diagnostic yield of CES as a first-tier genetic test in 128 consecutive pediatric patients addressed to a referral center in the North-East of France for a suspected genetic disorder, mainly an inborn error of metabolism between January 2016 and August 2020. CES was performed using the TruSight One (4811 genes) or the TruSight One expanded (6699 genes) panel on an Illumina sequencing platform. The median age was 6.5 years (IQR 2.0-12.0) with 43% of males (55/128), and the median disease duration was 7 months (IQR 1-47). In the whole analysis, the CES diagnostic yield was 55% (70/128). The median test-to-report time was 5 months (IQR 4-7). According to CES indications, the CES diagnostic yields were 81% (21/26) for hyperlipidemia, 75% (6/8) for osteogenesis imperfecta, 64% (25/39) for metabolic disorders, 39% (10/26) for neurological disorders, and 28% (8/29) for the subgroup of patients with miscellaneous conditions. Our results demonstrate the usefulness of a CES-based diagnosis as a first-tier genetic test to establish a molecular diagnosis in pediatric patients with a suspected genetic disorder with a median test-to-report time of 5 months. It highlights the importance of a close interaction between the pediatrician with expertise in genetic disorders and the molecular medicine physician to optimize both CES indication and interpretation. Diagnostic yield of clinical exome sequencing (CES) as a first-tier genetic test for diagnosing genetic disorders in 128 consecutive pediatric patients referred to a reference center in the North-East of France for a suspected genetic disorder, mainly an inborn error of metabolism between January 2016 and August 2020. The CES diagnostic yields are reported in the whole population and patients' subgroups (hyperlipidemia, osteogenesis imperfecta, metabolic diseases, neurological disorders, miscellaneous conditions) (Icons made by Flaticon, flaticon.com; CC-BY-3.0).
下一代测序的出现使得使用临床外显子组测序 (CES) 面板进行遗传疾病的经济高效且直接的诊断方法成为可能。我们进行了一项回顾性观察研究，以评估 CES 作为法国东北部一个转诊中心的 128 例疑似遗传疾病（主要为代谢性遗传疾病）患者的一线基因检测的诊断率，这些患者于 2016 年 1 月至 2020 年 8 月间就诊。CES 是在 Illumina 测序平台上使用 TruSight One（4811 个基因）或 TruSight One 扩展版（6699 个基因）面板进行的。中位年龄为 6.5 岁（IQR 2.0-12.0），男性占 43%（55/128），中位疾病持续时间为 7 个月（IQR 1-47）。在整个分析中，CES 的诊断率为 55%（70/128）。中位检测到报告的时间为 5 个月（IQR 4-7）。根据 CES 适应证，26 例高脂血症患者中 CES 的诊断率为 81%（21/26），8 例成骨不全症患者中 CES 的诊断率为 75%（6/8），39 例代谢性疾病患者中 CES 的诊断率为 64%（25/39），26 例神经疾病患者中 CES 的诊断率为 39%（10/26），29 例其他条件患者中 CES 的诊断率为 28%（8/29）。我们的结果证明了 CES 作为一线基因检测在疑似遗传疾病的儿科患者中建立分子诊断的有效性，中位检测到报告的时间为 5 个月。它强调了儿科医生与遗传疾病专家以及分子医学医生之间密切互动的重要性，以优化 CES 适应证和解释。
