Towards a Change in the Diagnostic Algorithm of Autism Spectrum Disorders: Evidence Supporting Whole Exome Sequencing as a First-Tier Test.
Towards a Change in the Diagnostic Algorithm of Autism Spectrum Disorders: Evidence Supporting Whole Exome Sequencing as a First-Tier Test.
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改变自闭症谱系诊断算法的变化：支持整个外显子组测序作为第一层测试的证据。
DOI：
10.3390/genes12040560
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发表时间：
2021-04-12
期刊：
影响因子：
3.5
通讯作者：
Alvarez-Mora MI
中科院分区：
文献类型：
--
作者：
Arteche-López A;Gómez Rodríguez MJ;Sánchez Calvin MT;Quesada-Espinosa JF;Lezana Rosales JM;Palma Milla C;Gómez-Manjón I;Hidalgo Mayoral I;Pérez de la Fuente R;Díaz de Bustamante A;Darnaude MT;Gil-Fournier B;Ramiro León S;Ramos Gómez P;Sierra Tomillo O;Juárez Rufián A;Arranz Cano MI;Villares Alonso R;Morales-Pérez P;Segura-Tudela A;Camacho A;Nuñez N;Simón R;Moreno-García M;Alvarez-Mora MI
自闭症谱系障碍（ASD）是一种流行的和极其异质性的神经发育障碍（NDD），具有很强的遗传成分。近年来，新生突变与ASD病因学的临床相关性已得到证实。目前的指南建议将染色体微阵列（CMA）和FMR 1检测作为第一级检测，但越来越多的证据支持使用NGS诊断NDD。特别是在ASD中，尚未对其进行广泛评估，因此，我们在343名ASD患者的队列中进行并比较了CMA，FMR 1检测和/或全外显子组测序（WES）的临床实用性。我们实现了12.8%（44/343）的全球诊断率，其中大多数以WES（33/44; 75%）为特征，而CMA（9/44; 20.4%）或FMR 1检测（2/44; 4.5%）。考虑到进行基因检测的年龄，我们在22.5%（37/164）的5岁以上患者中发现了因果性基因改变，但在该年龄以下的患者中仅为3.9%（7/179）。我们的数据证明了WES在ASD研究中的诊断能力高于CMA，并支持在没有脆性X综合征的怀疑时，将WES作为这种疾病遗传诊断的第一层测试。
Autism spectrum disorder (ASD) is a prevalent and extremely heterogeneous neurodevelopmental disorder (NDD) with a strong genetic component. In recent years, the clinical relevance of de novo mutations to the aetiology of ASD has been demonstrated. Current guidelines recommend chromosomal microarray (CMA) and a FMR1 testing as first-tier tests, but there is increasing evidence that support the use of NGS for the diagnosis of NDDs. Specifically in ASD, it has not been extensively evaluated and, thus, we performed and compared the clinical utility of CMA, FMR1 testing, and/or whole exome sequencing (WES) in a cohort of 343 ASD patients. We achieved a global diagnostic rate of 12.8% (44/343), the majority of them being characterised by WES (33/44; 75%) compared to CMA (9/44; 20.4%) or FMR1 testing (2/44; 4.5%). Taking into account the age at which genetic testing was carried out, we identified a causal genetic alteration in 22.5% (37/164) of patients over 5 years old, but only in 3.9% (7/179) of patients under this age. Our data evidence the higher diagnostic power of WES compared to CMA in the study of ASD and support the implementation of WES as a first-tier test for the genetic diagnosis of this disorder, when there is no suspicion of fragile X syndrome.
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