ABSTRACT

Introduction

Genetic testing of patients with clinically diagnosed or suspected primary immunodeficiencies (PIDs) constitutes standard of care. Choice of testing modality and patient attributes can impact the likelihood of securing a diagnosis.

Areas covered

Published diagnostic rates for gene panel testing, exome sequencing (WES), and whole genome sequencing are compared among cohorts identified within PubMed. Performance of the testing platforms is reviewed in PIDs taken as a whole, followed by separate cohorts of patients with suspected PIDs, specific PIDs, and clinical phenotypes that can be associated with underlying PIDs.

Expert opinion

Massively parallel high-throughput sequencing clearly represents the most expedient method for diagnosis of PIDs. For patients from highly consanguineous backgrounds, WES and whole genome sequencing should be performed to obtain optimal diagnostic yield. For patients for whom familial consanguinity is unlikely, choice of platform depends upon the phenotype. In patients with suspected PIDs, assessment for copy number variants is important, whether as part of gene panel bioinformatic analyses or combined with WES. Diagnostic rates overall for massively parallel sequencing are high for clinically diagnosed and suspected PIDs. WES may have a slightly higher overall yield, but gene panel testing represents a cost-effective and efficient reasonable initial step.

中文翻译：

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2020 年关于对原发性免疫缺陷患者使用基因检测的更新。

摘要

介绍

临床诊断或疑似原发性免疫缺陷 (PID) 患者的基因检测构成了护理标准。测试方式和患者属性的选择会影响获得诊断的可能性。

覆盖区域

在 PubMed 中确定的队列中比较已发布的基因面板测试、外显子组测序 (WES) 和全基因组测序的诊断率。测试平台的性能在 PID 中作为一个整体进行审查，然后是单独的疑似 PID、特定 PID 和可能与潜在 PID 相关的临床表型的患者队列。

专家意见

大规模并行高通量测序显然代表了诊断 PID 的最方便的方法。对于具有高度血缘背景的患者，应进行 WES 和全基因组测序以获得最佳诊断率。对于不太可能有家族血缘关系的患者，平台的选择取决于表型。对于疑似 PID 的患者，无论是作为基因面板生物信息学分析的一部分还是与 WES 相结合，对拷贝数变异的评估都很重要。对于临床诊断和疑似 PID，大规模并行测序的总体诊断率很高。WES 的总产量可能略高，但基因面板测试代表了一种经济高效且合理的初始步骤。