BACKGROUND Inborn errors of immunity (IEIs) are more than 500 different rare congenital disorders of the immune system characterized by susceptibility to infections and immune dysregulation. The significant overlap of the clinical features among the different forms may lead to diagnostic delay. High throughput sequencing techniques may allow a timely genetic definition. Guidelines for the use and the interpretation of genetic testing produced by the American College of Medical Genetics and Genomics (ACMG) and the European Society of Human Genetics (ESHG) do not cover specificities for the application to IEIs. OBJECTIVE The aim of this consensus study is to define the best approach to genetic testing for IEIs. METHODS A panel of experts in the context of the Italian Primary Immunodeficiency Network (IPINet) composed a list of statements that were evaluated using Delphi method. RESULTS The experts recommend that genetic testing for IEIs should be offered to selected patients with warning signs for IEIs and highlight the crucial role of thorough phenotyping and functional tests for the conclusive diagnosis of IEI. Comprehensive educational programs targeted to health care professionals and the public should be developed to increase IEIs awareness and reduce the diagnostic delay. Ethical issues should be pondered over the diagnostic advantages of genetic tests requested for diagnostic purposes. CONCLUSION Adherence to the guidelines on the use and interpretation of genetic testing for the diagnosis of IEIs should help limiting the inappropriate use of these techniques and reduce the risk of misdiagnosis and apprehension for inconclusive genetic results.

中文翻译：

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意大利原发性免疫缺陷网络关于使用和解释基因检测诊断先天性免疫缺陷 （IEI） 的共识。


背景 先天性免疫缺陷 （IEI） 是 500 多种不同的罕见先天性免疫系统疾病，其特征是易受感染和免疫失调。不同类型之间临床特征的显著重叠可能导致诊断延迟。高通量测序技术可能允许及时进行遗传定义。美国医学遗传学与基因组学学会 （ACMG） 和欧洲人类遗传学学会 （ESHG） 制定的基因检测的使用和解释指南未涵盖应用于 IEI 的特异性。目的 这项共识研究的目的是确定 IEI 基因检测的最佳方法。方法 意大利原发性免疫缺陷网络 （IPINet） 背景下的专家小组编写了一份使用 Delphi 方法进行评估的陈述清单。结果 专家建议，应向具有 IEI 警示体征的特定患者提供 IEI 基因检测，并强调全面的表型和功能检测对 IEI 的结论性诊断的关键作用。应制定针对医疗保健专业人员和公众的综合教育计划，以提高 IEI 意识并减少诊断延误。应考虑伦理问题，而不是为诊断目的而要求的基因检测的诊断优势。结论 遵守关于使用和解释基因检测诊断 IEI 的指南应该有助于限制这些技术的不当使用，并降低误诊和对不确定遗传结果的担忧的风险。