Department of Immunology, University Hospital Southampton NHSFT, Southampton, UK.
Southampton National Institute for Health Research Clinical Research Facility, University Hospital Southampton NHSFT, Southampton, UK.
Clin Genet. 2018 Mar;93(3):647-655. doi: 10.1111/cge.13163. Epub 2018 Feb 2.
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.
原发性免疫缺陷病（PID）是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 的表型广泛，发病率和死亡率较高，治疗选择往往较为复杂。随着下一代测序（NGS）的普及，PID 遗传病因的发现率呈指数级增长。确定潜在的单基因诊断为患者提供了重要的临床获益，有可能改变治疗方法、促进遗传咨询和植入前诊断。我们在一系列 PID 表型的临床护理中研究了一个包含 242 个基因的 NGS PID 面板。我们还评估了 Phenomizer 从人类表型本体（HPO）术语预测因果基因的能力。共招募了 27 名参与者，在 48%（13/27）的参与者中发现了 15 个可报告的变异。该面板结果对 37%（10/27）的参与者的治疗有影响。Phenomizer 从 HPO 术语中确定了携带变异的基因在 33%（9/27）的参与者中。这项研究表明，基因检测在 PID 护理中的临床效果。然而，它也突出了 PID 基因组学领域中基因面板的一些缺点，以及 PID 的 HPO 术语分配当前面临的挑战。
