Using medical exome sequencing to identify the causes of neurodevelopmental disorders: Experience of 2 clinical units and 216 patients
Using medical exome sequencing to identify the causes of neurodevelopmental disorders: Experience of 2 clinical units and 216 patients
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DOI：
10.1111/cge.13102
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发表时间：
2018-03-01
影响因子：
3.5
通讯作者：
Mignot, C.
中科院分区：
文献类型：
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作者：
Cherot, E.;Keren, B.;Mignot, C.
尽管全外显子组测序(WES)是诊断神经发育障碍(NDDS)的金标准，但对于一些遗传中心来说，它仍然很昂贵。由所有OMIM参考基因组成的商业化面板被称为医学外显子组(ME)，构成了WES的一种替代策略，但其效率鲜为人知。在这项研究中，我们报告了两个临床遗传中心使用ME诊断NDDS的经验。我们在两个法国遗传中心招募了216名符合单位日常实践的NDDS患者，包括非综合征性智能障碍(NSID，n=33)、综合征性ID(NSID=122)、儿童神经退行性疾病(n=7)和自闭症谱系障碍(ASD，n=54)。我们用Illumina TruSight One测序试剂盒对先证者及其父母(如果有)的样本进行了测序。我们在56个指标患者中发现了致病或可能致病的变异，全球诊断率为25.9%。以ID为主要诊断的患者的诊断率(32%)高于ASD患者(3.7%)。我们的结果表明，当WES不能作为常规诊断工具时，ME的使用对于ID患者是一种有价值的策略。
Although whole-exome sequencing (WES) is the gold standard for the diagnosis of neurodevelopmental disorders (NDDs), it remains expensive for some genetic centers. Commercialized panels comprising all OMIM-referenced genes called medical exome (ME) constitute an alternative strategy to WES, but its efficiency is poorly known. In this study, we report the experience of 2 clinical genetic centers using ME for diagnosis of NDDs. We recruited 216 consecutive index patients with NDDs in 2 French genetic centers, corresponded to the daily practice of the units and included non-syndromic intellectual disability (NSID, n=33), syndromic ID (NSID=122), pediatric neurodegenerative disorders (n=7) and autism spectrum disorder (ASD, n=54). We sequenced samples from probands and their parents (when available) with the Illumina TruSight One sequencing kit. We found pathogenic or likely pathogenic variants in 56 index patients, for a global diagnostic yield of 25.9%. The diagnosis yield was higher in patients with ID as the main diagnosis (32%) than in patients with ASD (3.7%). Our results suggest that the use of ME is a valuable strategy for patients with ID when WES cannot be used as a routine diagnosis tool.