Clinical efficacy of a next-generation sequencing gene panel for primary immunodeficiency diagnostics
Clinical efficacy of a next-generation sequencing gene panel for primary immunodeficiency diagnostics
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DOI：
10.1111/cge.13163
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发表时间：
2018-03-01
影响因子：
3.5
通讯作者：
Williams, A. P.
中科院分区：
文献类型：
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作者：
Rae, W.;Ward, D.;Williams, A. P.
原发性免疫缺陷（PID）是一种罕见的单基因先天性免疫缺陷，导致人体免疫系统功能受损。PID具有广泛的表型，发病率和死亡率增加，治疗选择通常很复杂。随着下一代测序（NGS）的可及性增加，PID遗传原因的发现率呈指数级增长。识别潜在的单基因诊断为患者提供了重要的临床益处，有可能改变治疗方法，促进遗传咨询和植入前诊断。我们研究了一系列PID表型的临床护理中的242个基因的NGS PID面板。我们还评估了Phenomizer从人类表型本体（HPO）术语预测因果基因。招募了27名参与者，在48%（13/27）的参与者中共识别出15种可报告变体。小组结果对37%（10/27）的参与者的治疗有影响。Phenomizer在33%（9/27）的参与者中从HPO术语中识别出携带变异的基因。这项研究显示了基因检测在PID护理中的临床疗效。然而，它也突出了PID基因组学快速发展领域中基因组的一些缺点，以及PID HPO术语分配的当前挑战。
Primary immunodeficiencies (PIDs) are rare monogenic inborn errors of immunity that result in impairment of functions of the human immune system. PIDs have a broad phenotype with increased morbidity and mortality, and treatment choices are often complex. With increased accessibility of next-generation sequencing (NGS), the rate of discovery of genetic causes for PID has increased exponentially. Identification of an underlying monogenic diagnosis provides important clinical benefits for patients with the potential to alter treatments, facilitate genetic counselling, and pre-implantation diagnostics. We investigated a NGS PID panel of 242 genes within clinical care across a range of PID phenotypes. We also evaluated Phenomizer to predict causal genes from human phenotype ontology (HPO) terms. Twenty-seven participants were recruited, and a total of 15 reportable variants were identified in 48% (13/27) of the participants. The panel results had implications for treatment in 37% (10/27) of participants. Phenomizer identified the genes harbouring variants from HPO terms in 33% (9/27) of participants. This study shows the clinical efficacy that genetic testing has in the care of PID. However, it also highlights some of the disadvantages of gene panels in the rapidly moving field of PID genomics and current challenges in HPO term assignment for PID.