PDF(Pubmed)
Abstract：
BACKGROUND: Genetic disorders often manifest as abnormal fetal or childhood development. Copy number variations (CNVs) represent a significant genetic mechanism underlying such disorders. Despite their importance, the effectiveness of clinical exome sequencing (CES) in detecting CNVs, particularly small ones, remains incompletely understood. We aimed to evaluate the detection of both large and small CNVs using CES in a substantial clinical cohort, including parent-offspring trios and proband only analysis.
METHODS: We conducted a retrospective analysis of CES data from 2428 families, collected from 2018 to 2021. Detected CNV were categorized as large or small, and various validation techniques including chromosome microarray (CMA), Multiplex ligation-dependent probe amplification assay (MLPA), and/or PCR-based methods, were employed for cross-validation.
RESULTS: Our CNV discovery pipeline identified 171 CNV events in 154 cases, resulting in an overall detection rate of 6.3%. Validation was performed on 113 CNVs from 103 cases to assess CES reliability. The overall concordance rate between CES and other validation methods was 88.49% (100/113). Specifically, CES demonstrated complete consistency in detecting large CNV. However, for small CNVs, consistency rates were 81.08% (30/37) for deletions and 73.91% (17/23) for duplications.
CONCLUSIONS: CES demonstrated high sensitivity and reliability in CNV detection. It emerges as an economical and dependable option for the clinical CNV detection in cases of developmental abnormalities, especially fetal structural abnormalities.
METHODS: We conducted a retrospective analysis of CES data from 2428 families, collected from 2018 to 2021. Detected CNV were categorized as large or small, and various validation techniques including chromosome microarray (CMA), Multiplex ligation-dependent probe amplification assay (MLPA), and/or PCR-based methods, were employed for cross-validation.
RESULTS: Our CNV discovery pipeline identified 171 CNV events in 154 cases, resulting in an overall detection rate of 6.3%. Validation was performed on 113 CNVs from 103 cases to assess CES reliability. The overall concordance rate between CES and other validation methods was 88.49% (100/113). Specifically, CES demonstrated complete consistency in detecting large CNV. However, for small CNVs, consistency rates were 81.08% (30/37) for deletions and 73.91% (17/23) for duplications.
CONCLUSIONS: CES demonstrated high sensitivity and reliability in CNV detection. It emerges as an economical and dependable option for the clinical CNV detection in cases of developmental abnormalities, especially fetal structural abnormalities.
摘要：
背景：遗传性疾病常表现为胎儿或儿童发育异常。拷贝数变异（CNV）代表了这种疾病的重要遗传机制。尽管它们很重要,临床外显子组测序（CES）在检测CNVs中的有效性，特别是小的，仍然不完全理解。我们的目的是在大量临床队列中使用CES评估大型和小型CNV的检测，包括亲子关系三重奏和先证者分析。
方法：我们对来自2428个家庭的CES数据进行了回顾性分析，从2018年到2021年收集。检测到的CNV分为大或小，和各种验证技术，包括染色体微阵列（CMA），多重连接依赖性探针扩增测定（MLPA），和/或基于PCR的方法，被用于交叉验证。
结果：我们的CNV发现管道在154例中确定了171个CNV事件，总体检出率为6.3%。对103例病例的113例CNV进行了验证，以评估CES的可靠性。CES与其他验证方法的总体符合率为88.49%(100/113)。具体来说,CES在检测大CNV方面表现出完全的一致性。然而,对于小型CNVs，缺失的一致性率为81.08%(30/37),重复的一致性率为73.91%(17/23).
结论：CES在CNV检测中表现出高灵敏度和可靠性。在发育异常的情况下，它是临床CNV检测的一种经济可靠的选择，尤其是胎儿结构异常.
方法：我们对来自2428个家庭的CES数据进行了回顾性分析，从2018年到2021年收集。检测到的CNV分为大或小，和各种验证技术，包括染色体微阵列（CMA），多重连接依赖性探针扩增测定（MLPA），和/或基于PCR的方法，被用于交叉验证。
结果：我们的CNV发现管道在154例中确定了171个CNV事件，总体检出率为6.3%。对103例病例的113例CNV进行了验证，以评估CES的可靠性。CES与其他验证方法的总体符合率为88.49%(100/113)。具体来说,CES在检测大CNV方面表现出完全的一致性。然而,对于小型CNVs，缺失的一致性率为81.08%(30/37),重复的一致性率为73.91%(17/23).
结论：CES在CNV检测中表现出高灵敏度和可靠性。在发育异常的情况下，它是临床CNV检测的一种经济可靠的选择，尤其是胎儿结构异常.
