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Abstract：
As the application of next generation sequencing (NGS) is moving to earlier stages in the diagnostic pipeline for primary immunodeficiencies (PIDs), re-evaluation of its effectiveness is required. The aim of this study is to systematically review the diagnostic yield of NGS in PIDs.
PubMed and Embase databases were searched for relevant studies. Studies were eligible when describing the use of NGS in patients that had previously been diagnosed with PID on clinical and/or laboratory findings. Relevant data on study characteristics, technological performance and diagnostic yield were extracted.
Fourteen studies were eligible for data extraction. Six studies described patient populations from specific PID subcategories. The remaining studies included patients with unsorted PIDs. The studies were based on populations from Italy, Iran, Turkey, Thailand, the Netherlands, Norway, Saudi Arabia, Sweden, the UK, and the USA. Eight studies used an array-based targeted gene panel, four used WES in combination with a PID filter, and two used both techniques. The mean reported reading depth ranged from 98 to 1337 times. Five studies described the sensitivity of the applied techniques, ranging from 83 to 100%, whereas specificity ranged from 45 to 99.9%. The percentage of patients who were genetically diagnosed ranged from 15 to 79%. Several studies described clinical implications of the genetic findings.
NGS has the ability to contribute significantly to the identification of molecular mechanisms in PID patients. The diagnostic yield highly depends on population and on the technical circumstances under which NGS is employed. Further research is needed to determine the exact diagnostic yield and clinical implications of NGS in patients with PID.
PubMed and Embase databases were searched for relevant studies. Studies were eligible when describing the use of NGS in patients that had previously been diagnosed with PID on clinical and/or laboratory findings. Relevant data on study characteristics, technological performance and diagnostic yield were extracted.
Fourteen studies were eligible for data extraction. Six studies described patient populations from specific PID subcategories. The remaining studies included patients with unsorted PIDs. The studies were based on populations from Italy, Iran, Turkey, Thailand, the Netherlands, Norway, Saudi Arabia, Sweden, the UK, and the USA. Eight studies used an array-based targeted gene panel, four used WES in combination with a PID filter, and two used both techniques. The mean reported reading depth ranged from 98 to 1337 times. Five studies described the sensitivity of the applied techniques, ranging from 83 to 100%, whereas specificity ranged from 45 to 99.9%. The percentage of patients who were genetically diagnosed ranged from 15 to 79%. Several studies described clinical implications of the genetic findings.
NGS has the ability to contribute significantly to the identification of molecular mechanisms in PID patients. The diagnostic yield highly depends on population and on the technical circumstances under which NGS is employed. Further research is needed to determine the exact diagnostic yield and clinical implications of NGS in patients with PID.
摘要：
随着下一代测序（NGS）的应用正在进入原发性免疫缺陷（PID）诊断流程的早期阶段，需要对其有效性进行重新评估。这项研究的目的是系统地回顾NGS在PID中的诊断率。
搜索PubMed和Embase数据库以进行相关研究。当描述在先前根据临床和/或实验室发现诊断为PID的患者中使用NGS时，研究合格。有关研究特征的相关数据，提取了技术性能和诊断产量。
14项研究符合数据提取条件。六项研究描述了来自特定PID子类别的患者群体。其余研究包括患有未分类PID的患者。这些研究是基于意大利的人群，伊朗,土耳其,泰国,荷兰,挪威,沙特阿拉伯,瑞典,英国,和美国。八项研究使用了基于阵列的靶向基因面板，四个与PID过滤器结合使用的WES，两个人使用了这两种技术。平均报告的阅读深度为98至1337倍。五项研究描述了应用技术的敏感性，从83％到100％，而特异性范围为45-99.9%。被基因诊断的患者的百分比范围为15％至79％。一些研究描述了遗传发现的临床意义。
NGS能够显著促进PID患者分子机制的鉴定。诊断结果高度取决于人口和使用NGS的技术环境。需要进一步的研究来确定NGS在PID患者中的确切诊断率和临床意义。
搜索PubMed和Embase数据库以进行相关研究。当描述在先前根据临床和/或实验室发现诊断为PID的患者中使用NGS时，研究合格。有关研究特征的相关数据，提取了技术性能和诊断产量。
14项研究符合数据提取条件。六项研究描述了来自特定PID子类别的患者群体。其余研究包括患有未分类PID的患者。这些研究是基于意大利的人群，伊朗,土耳其,泰国,荷兰,挪威,沙特阿拉伯,瑞典,英国,和美国。八项研究使用了基于阵列的靶向基因面板，四个与PID过滤器结合使用的WES，两个人使用了这两种技术。平均报告的阅读深度为98至1337倍。五项研究描述了应用技术的敏感性，从83％到100％，而特异性范围为45-99.9%。被基因诊断的患者的百分比范围为15％至79％。一些研究描述了遗传发现的临床意义。
NGS能够显著促进PID患者分子机制的鉴定。诊断结果高度取决于人口和使用NGS的技术环境。需要进一步的研究来确定NGS在PID患者中的确切诊断率和临床意义。
