Emil E. Vorsteveld , Caspar I. Van der Made , Sanne P. Smeekens , Janneke H. Schuurs-Hoeijmakers , Galuh Astuti , Heleen Diepstra , Christian Gilissen , Evelien Hoenselaar , Alice Janssen , Kees van Roozendaal , Jettie Sikkema-van Engelen , Wouter Steyaert , Marjan M. Weiss , Helger G. Yntema , Tuomo Mantere , Mofareh S. AlZahrani , Koen van Aerde , Beata Derfalvi , Eissa Ali Faqeih , Stefanie S.V. Henriet , Alexander Hoischen
{"title":"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。","authors":"Emil E. Vorsteveld , Caspar I. Van der Made , Sanne P. Smeekens , Janneke H. Schuurs-Hoeijmakers , Galuh Astuti , Heleen Diepstra , Christian Gilissen , Evelien Hoenselaar , Alice Janssen , Kees van Roozendaal , Jettie Sikkema-van Engelen , Wouter Steyaert , Marjan M. Weiss , Helger G. Yntema , Tuomo Mantere , Mofareh S. AlZahrani , Koen van Aerde , Beata Derfalvi , Eissa Ali Faqeih , Stefanie S.V. Henriet , Alexander Hoischen","doi":"10.1016/j.clim.2024.110375","DOIUrl":null,"url":null,"abstract":"<div><div>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 <em>in silico</em> 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.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"268 ","pages":"Article 110375"},"PeriodicalIF":4.5000,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Clinical exome sequencing data from patients with inborn errors of immunity: Cohort level diagnostic yield and the benefit of systematic reanalysis\",\"authors\":\"Emil E. Vorsteveld , Caspar I. Van der Made , Sanne P. Smeekens , Janneke H. Schuurs-Hoeijmakers , Galuh Astuti , Heleen Diepstra , Christian Gilissen , Evelien Hoenselaar , Alice Janssen , Kees van Roozendaal , Jettie Sikkema-van Engelen , Wouter Steyaert , Marjan M. Weiss , Helger G. Yntema , Tuomo Mantere , Mofareh S. AlZahrani , Koen van Aerde , Beata Derfalvi , Eissa Ali Faqeih , Stefanie S.V. Henriet , Alexander Hoischen\",\"doi\":\"10.1016/j.clim.2024.110375\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>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 <em>in silico</em> 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.</div></div>\",\"PeriodicalId\":10392,\"journal\":{\"name\":\"Clinical immunology\",\"volume\":\"268 \",\"pages\":\"Article 110375\"},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2024-10-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1521661624004844\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical immunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1521661624004844","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
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.
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.