先天性免疫错误患者的临床外显子组测序数据:队列水平的诊断率和系统性再分析的益处。

IF 4.5 3区 医学 Q2 IMMUNOLOGY Clinical immunology Pub Date : 2024-10-05 DOI:10.1016/j.clim.2024.110375
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引用次数: 0

摘要

虽然新一代测序技术拓展了人们对先天性免疫错误(IEI)的科学认识,但外显子组测序技术的临床应用和再利用仍处于起步阶段。我们使用最新的硅学 IEI 基因面板重新研究了 1300 例 IEI 患者的临床外显子组数据。通过专家审查对变异进行了分类和策划。标准外显子组分析后的分子诊断率为 11.8%。通过系统性再分析,我们在 5.2% 的未确诊患者中发现了感兴趣的变异,其中 76.7% 是(候选)致病变异,为 15.2% 的患者提供了(候选)诊断。我们发现确诊的分子诊断率提高了 1.7 个百分点。我们发现基因诊断患者的可操作性很高(76.4%)。尽管诊断的绝对收益不大,但这些数据支持了对 IEI 患者进行外显子组迭代再分析的益处,并传达了这样一个理念:我们目前对 IEI 相关基因和变异的了解还远远没有达到饱和。
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Clinical exome sequencing data from patients with inborn errors of immunity: Cohort level diagnostic yield and the benefit of systematic reanalysis
While next generation sequencing has expanded the scientific understanding of Inborn Errors of Immunity (IEI), the clinical use and re-use of exome sequencing is still emerging. We revisited clinical exome data from 1300 IEI patients using an updated in silico IEI gene panel. Variants were classified and curated through expert review. The molecular diagnostic yield after standard exome analysis was 11.8 %. Through systematic reanalysis, we identified variants of interest in 5.2 % of undiagnosed patients, with 76.7 % being (candidate) disease-causing, providing a (candidate) diagnosis in 15.2 % of our cohort. We find a 1.7 percentage point increase in conclusive molecular diagnoses. We find a high degree of actionability in patients with a genetic diagnosis (76.4 %). Despite the modest absolute diagnostic gain, these data support the benefit of iterative exome reanalysis in IEI patients, conveying the notion that our current understanding of genes and variants involved in IEI is by far not saturated.
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来源期刊
Clinical immunology
Clinical immunology 医学-免疫学
CiteScore
12.30
自引率
1.20%
发文量
212
审稿时长
34 days
期刊介绍: Clinical Immunology publishes original research delving into the molecular and cellular foundations of immunological diseases. Additionally, the journal includes reviews covering timely subjects in basic immunology, along with case reports and letters to the editor.
期刊最新文献
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