Clinical exome sequencing data from patients with inborn errors of immunity Cohort level diagnostic yield and the benefit of systematic reanalysis

Clinical exome sequencing data from patients with inborn errors of immunity : Cohort level diagnostic yield and the benefit of systematic reanalysis

Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 268(2024) vom: 12. Nov., Seite 110375
1. Verfasser: Vorsteveld, Emil E (VerfasserIn)
Weitere Verfasser: Van der Made, Caspar I (BerichterstatterIn), Smeekens, Sanne P (BerichterstatterIn), Schuurs-Hoeijmakers, Janneke H (BerichterstatterIn), Astuti, Galuh (BerichterstatterIn), Diepstra, Heleen (BerichterstatterIn), Gilissen, Christian (BerichterstatterIn), Hoenselaar, Evelien (BerichterstatterIn), Janssen, Alice (BerichterstatterIn), van Roozendaal, Kees (BerichterstatterIn), Engelen, Jettie Sikkema-van (BerichterstatterIn), Steyaert, Wouter (BerichterstatterIn), Weiss, Marjan M (BerichterstatterIn), Yntema, Helger G (BerichterstatterIn), Mantere, Tuomo (BerichterstatterIn), AlZahrani, Mofareh S (BerichterstatterIn), van Aerde, Koen, Derfalvi, Beata, Faqeih, Eissa Ali, Henriet, Stefanie S V, van Hoof, Elise, Idressi, Eman, Issekutz, Thomas B, Jongmans, Marjolijn C J, Keski-Filppula, Riikka, Krapels, Ingrid, Te Loo, Maroeska, Mulders-Manders, Catharina M, Ten Oever, Jaap, Potjewijd, Judith, Sarhan, Nora Tarig, Slot, Marjan C, Terhal, Paulien A, Thijs, Herman, Vandersteen, Anthony, Vanhoutte, Els K, van de Veerdonk, Frank, van Well, Gijs, Netea, Mihai G, all members of the Radboud University Medical Center multidisciplinary immune-disease board, Simons, Annet, Hoischen, Alexander, Arts, Rob J W, Bijker, Else M, Bruno, Mariolina, Hobo, Willemijn, Hoppenreijs, Esther, de Jonge, Marien I, van Laarhoven, Arjan, van der Molen, Renate, Oud, Manon, Schatorje, Ellen J H, Smeets, Ruben, Sprenkeler, Evelien G G, Stol, Kim, Verhagen, Lilly M, Zonneveld-Huijssoon, Evelien
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2024
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Autoimmune disorders Autoinflammatory disorders Clinical exome sequencing Exome reanalysis Genomics Inborn errors of immunity Longitudinal follow-up NGS-based sequencing Primary immunodeficiencies
Beschreibung
Zusammenfassung:Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.
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
Beschreibung:Date Completed 04.11.2024
Date Revised 04.11.2024
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2024.110375